The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple ...The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells （ECs） which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells （EPCs） are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genornic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.展开更多
By means of the tension determination of rat thoracic aortic ring. it was found that PAF depressed the acetylcholine (Ach)-induced relaxation of the rings, having undergone 20 min of deoxygenation followed by 30 min o...By means of the tension determination of rat thoracic aortic ring. it was found that PAF depressed the acetylcholine (Ach)-induced relaxation of the rings, having undergone 20 min of deoxygenation followed by 30 min of reoxygenation, to 36. 1% of norepinephine(NE) precontraction. PAF receptor antagonist WEB 2170 markedly improved the Ach-induced relaxation of the brief deoxygenated and reoxygenated rings to 86. 7 % of NE precontraction. The results indicated that PAF may be one of the mediators involved in the endothelium relaxation dysfunction related to brief deoxygenation and reoxygenation, and that PAF antagonist WEB 2170 has the protective effect on endothelium relaxation function.展开更多
Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity...Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.展开更多
Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells wer...Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).展开更多
Background Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension(PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the...Background Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension(PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation and apoptosis balance. However, the molecular mechanism underlying of this balance is still unknown. Methods To clarify the biological effects of hypoxic air exposure and hypoxia-inducible factor-1α(HIF-1α) on pulmonary arterial smooth muscle cell(PASMC) and pulmonary arterial hypertension rats, the cells were cultured in a hypoxic chamber under oxygen concentrations. Cell viability, reactive oxygen species level, cell death, mitochondrial morphology, mitochondrial membrane potential, mitochondrial function and mitochondrial biosynthesis, as well as fission-and fusion-related proteins, were measured under hypoxic conditions. In addition, rats were maintained under hypoxic conditions, and the right ventricular systolic pressure, right ventricular hypertrophy index and right ventricular weight/body weight ratio were examined and recorded. Further, we assessed the role of HIF-1α in the development and progression of PH using HIF-1α gene knockdown using small interfering RNA transfection. Mdivi-1 treatment was performed before hypoxia to inhibit dynamin-related protein 1(Drp1). Results We found that HIF-1α expression was increased during hypoxia, which was crucial for hypoxia-induced mitochondrial dysfunction and hypoxia-stimulated PASMCs proliferation and apoptosis. We also found that targeting mitochondrial fission Drp1 by mitochondrial division inhibitor Mdivi-1 was effective in PH model rats. The results showed that mitochondrial dynamics were involved in the pulmonary vascular remodeling under hypoxia in vivo and in vitro. Furthermore, HIF-1α also modulated mitochondrial dynamics in pulmonary vascular remodeling under hypoxia through directly regulating the expression of Drp1. Conclusions In conclusion, our data suggests that abnormal mitochondrial dynamics could be a marker for the early diagnosis of PH and monitoring disease progression. Further research is needed to study the signaling pathways that govern mitochondrial fission/fusion in PH.展开更多
From a population of about 3500 single plants in Arabidopsis promoter trapping bank, one plant whose GUS-gene had been specifically expressed in vascular bundle, was screened by the method of gus tissue staining. The ...From a population of about 3500 single plants in Arabidopsis promoter trapping bank, one plant whose GUS-gene had been specifically expressed in vascular bundle, was screened by the method of gus tissue staining. The T-DNA flanking sequence was amplified using TAIL-PCR. This band will be purified and connected to TA cloning vector. After sequencing and searching in the genebank, its function will be demonatrated through transformation.展开更多
BACKGROUND: This study aims to evaluate the results of studies investigating neutrophilto-lymphocyte ratio(NLR) and to identify the prognostic and diagnostic value of NLR in occlusive vascular diseases.METHODS: With t...BACKGROUND: This study aims to evaluate the results of studies investigating neutrophilto-lymphocyte ratio(NLR) and to identify the prognostic and diagnostic value of NLR in occlusive vascular diseases.METHODS: With the aim of identifying the studies related to NLR, a search was performed on http://www.ncbi.nlm.nih.gov/pubmed by using the key words "neutrophil lymphocyte ratio" between January 2005 and December 2014. All of the original articles were evaluated according to date of publications, countries, clinics and topics. Studies about occlusive vascular diseases were evaluated according to their qualifications, review methods and results. SPSS for Windows 16.0 was used in data analysis and data were expressed as mean, standard deviation and percentage.RESULTS: A total of 735 original research articles were investigated. The number of publications have shown a regular logarithmic increase over the years. Thirty-two percent of all publications were performed by clinics in Turkey and 56.4% were performed by general-oncological surgery and cardiology clinics. A total of 107 publications were identified to be about occlusive vascular diseases, 80.3% of these publications were found to be prognostic and 19.6% to be diagnostic, 82.2% of them were found to be planned as retrospective and 17.7% as prospective. In 95.3% of prognostic publications, there was a positive correlation between high NLR values at admission and poor prognosis. In 95.3% of diagnostic publications high NLR values at admission were identifi ed to be signifi cant diagnostically.CONCLUSION: Elevated neutrophil-to-lymphocyte ratio at admission, could be used as a diagnostic and/or prognostic parameter in occlusive vascular diseases.展开更多
Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicate...Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.展开更多
BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery re...BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.展开更多
Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS)...Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS), and has become one of the most important causes of death for intensive care units(ICU) patients. Currently, although there has been some progress in knowledge of the pathogenesis of these vascular disorders, the detailed mechanisms remain unclear, and effective prophylaxis and treatment are still lacking. In this study, we aimed to provide a review of the literature regarding the regulatory mechanisms and prophylaxis as well as the treatment of vascular leakage in critical diseases such as severe trauma and shock, which could be beneficial for the overall clinical treatment of vascular leakage disorders.展开更多
Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manu...Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.展开更多
Objective. To determine whether serum vascular endothelial growth factor(VEGF)concentrations are altered in several kinds of coronary heart disease patients. Materials and methods. Using a VEGF enzyme-linked immunosor...Objective. To determine whether serum vascular endothelial growth factor(VEGF)concentrations are altered in several kinds of coronary heart disease patients. Materials and methods. Using a VEGF enzyme-linked immunosorbent assay(ELISA), serum VEGF concentrations were determined in antecubital venous blood of 16 patients with stable angina pectoris(SAP), 16 with unstable angina pectoris(UAP) and 16 with acute myocardial infarction(AMI) before and after thrombolytic therapy, and of 16 age- and sex-matched healthy volunteers who used as controls. Results. The concentrations of serum VEGF in patients with SAP(9860±2699pg/ml) and UAP (10361±2489pg/ml) tended to be higher than those in control subjects(8044±2457pg/ml), but the differences did not reach statistical significance (P>005 for each). Before thrombolytic therapy, the concentrations of serum VEGF in patients with AMI (28592±12515pg/ml) were significantly higher than those in patients with SAP, UAP or control subjects (P<001,respectively), and correlated with synchronous serum creatine kinase (CK) and its MB isoenzyme (CK-MB) contents(r=0866,P<0001 and r=0948,P<0001;respectively). Three hours after thrombolysis, the concentrations of VEGF had fallen to 11157±3129pg/ml (P<001 vs. before thrombolytic therapy and P<005 vs.control subjects). Conclusion. The present study shows that serum concentrations of VEGF in patients with AMI are markedly elevated and that increased serum VEGF levels may be one of the most sensitive indexes in diagnosing AMI and judging reperfusion.展开更多
Background In type 2 diabetes mellitus （T2DM）, high-density lipoprotein （HDL） impairs its anti-atherogenic properties and even develops to a pro-inflammatory and pro-atherogenic phenotype because of abnormal compo...Background In type 2 diabetes mellitus （T2DM）, high-density lipoprotein （HDL） impairs its anti-atherogenic properties and even develops to a pro-inflammatory and pro-atherogenic phenotype because of abnormal compositions and modifications. In this study, we ex- amined the effects and the related mechanisms of glycation of HDL on the proliferation and migration of vascular smooth muscle cells （VSMCs）. Methods ＆ Results Glycated HDL （G-HDL） was modified with D-glucose （25 mmol/L） in vitro. Diabetic HDL （D-HDL） was isolated from T2DM patients. Rat VSMCs were isolated from the thoracic aortas. Human VSMCs were obtained from ScienCell Research Laboratories. Alpha-actin was detected through immunofiuorescence. VSMC proliferation was assayed by Cell Count. VSMC migration was determined by transwell chamber and scratch-wound assay. Intracellular reactive oxygen species （ROS） was detected based on ROS-medi- ated 2＇,7＇-dichlorofluorescein （DCFH-DA） fluorescence. Compared to native HDL （N-HDL）, G-HDL remarkably promoted VSMC prolif- eration and migration in the dose and time-dependent manners. In addition, G-HDL enhanced ROS generation in VSMCs. However, the ROS scavenger, N-acetylcysteine, efficiently decreased ROS production and subsequently inhibited the proliferation of VSMCs induced by G-HDL. Similarly, D-HDL from T2DM patients also promoted ROS release and VSMC proliferation and migration. Conclusions HDL either glycated in vitro or isolated from T2DM patients triggered VSMC proliferation, migration, and oxidative stress. These results might partly interpret the higher morbidity of cardiovascular disease in T2DM patients.展开更多
Efficient strategies to promote microvascularization in vascular tissue engineering,a central priority in regenerative medicine,are still scarce;nano-and micro-sized aggregates and spheres or beads harboring primitive...Efficient strategies to promote microvascularization in vascular tissue engineering,a central priority in regenerative medicine,are still scarce;nano-and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering.Capillaries are the smallest type and in numerous blood vessels,which are distributed densely in cardiovascular system.To mimic this microvascular network,specific cell components and proangiogenic factors are required.Herein,advanced biofabrication methods in microvascular engineering,including extrusion-based and droplet-based bioprinting,Kenzan,and biogripper approaches,are deliberated with emphasis on the newest works in prevascular nano-and micro-sized aggregates and microspheres/microbeads.展开更多
BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at...BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.METHODS： A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly： a control group （S group, n=32） and a MSCs treatment group （M group, n=32）. 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 （baseline）, 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.RESULTS： In the lung tissue, VEGF decreased gradually in the S group （P〈0.05） and signi？ cantly decreased in the M group （P〈0.05）, but it increased more signi？ cantly than the values at the corresponding time points （P〈0.05）. In peripheral blood, VEGF increased gradually in the S group （P〈0.05） and markedly increased in the M group （P〈0.05）, but it decreased more signi？ cantly than the values at corresponding time points （P〈0.05）.CONCLUSION： MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.展开更多
To investigate the dynamic changes of serum vascular endothelial growth factor(VEGF) levels in a rat model of acute myocardial infarction. Materials and methods.Eighty eight adult male Sprague Dawley rats weighing app...To investigate the dynamic changes of serum vascular endothelial growth factor(VEGF) levels in a rat model of acute myocardial infarction. Materials and methods.Eighty eight adult male Sprague Dawley rats weighing approximately 270 g were used in this study. Eighty rats were subjected to left coronary artery ligation, with 8 rats for each different duration of infarct. Eight sham operated animals in which the left coronary artery was surgically exposed without ligation were used as controls. Blood samples were drawn from the right atrium before (sham animals) and 1,3,6,12,24 h and 2,3,5,7,14 d after myocardial infarction. The concentrations of serum VEGF were measured by a sensitive enzyme linked immunosorbent assay with a rabbit polyclonal antibody specific for VEGF. Results. In the 8 control animals, the mean concentration of serum VEGF was 66.99±17.83 pg/ml. Six hours after myocardial infarction, the level of serum VEGF significantly increased to 125.68±28.07 pg/ml (P<0.01 vs. sham controls), and reached a peak (240.61±70.63 pg/ml. P<0.01 vs. sham animals) at 24 h after ligation and then decreased gradually over the remaining 2 weeks. However, the level remained significantly elevated for 14 d (107.64±30.13pg/ml, P<0.01 vs. sham controls). Conclusion. The present study shows that the levels of serum VEGF are markedly increased until 14 d in the rat model of acute myocardial infarction. The increased serum VEGF level may play an important role in the angiogenesis associated with myocardial infarction.展开更多
Objective To construct the zinc finger protein-activating transcription factor (ZFP-ATF) plasmid and evaluate its efficacy in inducing vascular endothelial growth factor (VEGF) expression in EY.HY926 endothelial cells...Objective To construct the zinc finger protein-activating transcription factor (ZFP-ATF) plasmid and evaluate its efficacy in inducing vascular endothelial growth factor (VEGF) expression in EY.HY926 endothelial cells. Methods Firstly, we constructed the ZFP-ATF plasmid, then testified the quantity of VEGF protein in EY.HY926 endothelial cells after transfected with ZFP-ATP plasmid by Western blot, finally, we used the RT-PCR to testify whether the ZFP-ATF can stimulate expression of VEGF splice variants. Results The ZFP-ATF DNA sequences were located the multiclone sites of PVAX1 vector between the site of BamH Ⅰ and Xhol. Western blot result showed VEGF expression in EY.HY926 endothelial cells transfected with ZFP-ATF plasmid was significantly higher than that in cells transfected with VEGF165 (19.95±3.95 vs. 12.15±1.55 μg/μL, P<0.01). RT-PCR result showed VEGF-A mRNA expression level induced by ZFP-ATF was high than that induced by VEGF165. Conclusion ZFP-ATF can up-regulate the VEGF-A expression in comparison with VEGF165, which might have beneficial effects in angiogenesis process.展开更多
Objective To study the role of sirtuin 1 （SIRT1） in Fas ligand （FasL） expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were d...Objective To study the role of sirtuin 1 （SIRT1） in Fas ligand （FasL） expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell （VSMC） lysate. Smooth muscle cell （SMC）-specific human SIRT1 transgenic （Tg） C57BL/6 mice and their littermate wild-type （WT） controls underwent complete carotid artery ligation （ligation groups） or the ligation-excluded operation （sham groups）. The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 （SIRT1H363Y）, and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation （P〈0.001） and VSMCs treated with serum （P〈0.05 at the transcriptional level, P〈0.001 at the protein level）. No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL （P〈0.001）. The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 （P〈0.001）, while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 （P〈0.001）. Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.展开更多
To observe the regulating effects of vascular endothelial growth factor (VEGF) and angiotensinⅡ (ANG II) on the frog’s pericardium, lymphatic stomata and angiogenesis so as to reveal their effects and mechanism on t...To observe the regulating effects of vascular endothelial growth factor (VEGF) and angiotensinⅡ (ANG II) on the frog’s pericardium, lymphatic stomata and angiogenesis so as to reveal their effects and mechanism on the mesothelial permeability, lymphatic stoma regulation and myocardial hypertrophy. Methods. VEGF and ANGⅡ were injected into the frog’s peritoneal cavity so as to examine the changes of the pericardial stromata by using transmission electron microscopy, scanning electron microscopy and computerized imaging analysis. Results. Scattered distributed pericardial stomata were found on the parietal pericardium of the frog with a few sinusoid mesothelial cells, whose blood supply was directly from the cardiac chambers flowing into the trabecular spaces of the myocardium (because there are no blood vessels in the myocardium of the frog). The average diameters of the pericardial stomata in VEGF and ANGⅡ groups were 1.50μ m and 1.79μ m respectively, which were much larger than those in the control group (0.72μ m, P Conclusions. VEGF and ANGⅡ could strongly regulate the pericardial stomata by increasing their numbers and openings with larger diameters and higher distribution density. They could also increase the sinusoid areas with the result of the higher permeability of the pericardium, which clearly indicated that VEGF and ANGⅡ could speed up the material transfer of the pericardial cavity and play an important role in preventing myocardial interstitial edema. Yet there was no strong evidence to show the angiogenesis in the myocardium.展开更多
Diepithelialized tissue flap(DTF)with vascular anastomosis was de-signed in August 1987,and was used for the repair of 12 cases of large intraoraltissue defect.All the operations were successful.The clinical data were...Diepithelialized tissue flap(DTF)with vascular anastomosis was de-signed in August 1987,and was used for the repair of 12 cases of large intraoraltissue defect.All the operations were successful.The clinical data were reportedand the procedure to incise and transplant a DTF described.When the healingprocess and changes of DTF after transplantation were observed,it was foundthat a layer of new smooth epidermis was formed on the surface of the DTF.Theorigin of this new epidermis was discussed.Ten out of the 12 cases have been fol-lowed up for from half a year to 2 and a half years,and the results weresatisfactory.The new epidermis showed no hair growth and the patients did nothave any rough feeling,which usually occurred after ordinary skin grafting.It isbelieved that DTF transplantation is likely an ideal method for the repair andreconstruction of intraoral soft tissue defect.Its disadvantage was that the DTFcontracted severely after healing.Finally the authors put forward the problemsconcerning the transplantation of DTF,which should be investigated further.展开更多
基金The researches described in this article were partially supported by grants from the National Natural Science Foundation of China （No. 81570271 and 81400357） and NIH （UL1 RR024996）. We are very grateful to John R Lee （Assistant Professor of Medicine, Weill Comell Medical College, New York）, and Jeff J Zhu （Research Manager, Weill Comell Medical College, New York） for critical review of the article. The authors have nothing to disclosure.
文摘The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells （ECs） which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells （EPCs） are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genornic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.
文摘By means of the tension determination of rat thoracic aortic ring. it was found that PAF depressed the acetylcholine (Ach)-induced relaxation of the rings, having undergone 20 min of deoxygenation followed by 30 min of reoxygenation, to 36. 1% of norepinephine(NE) precontraction. PAF receptor antagonist WEB 2170 markedly improved the Ach-induced relaxation of the brief deoxygenated and reoxygenated rings to 86. 7 % of NE precontraction. The results indicated that PAF may be one of the mediators involved in the endothelium relaxation dysfunction related to brief deoxygenation and reoxygenation, and that PAF antagonist WEB 2170 has the protective effect on endothelium relaxation function.
基金supported by the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065),the Innovation Groups of NSFC(81721001),and the Young Scientists Fund(82102279).
文摘Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
基金supported by the Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)the Key Basic Research Projects of the Foundation Strengthening Plan(2022-JCJQZD-096-00)+2 种基金the National Key Research and Development Program of China(2022YFA1104604)the National Natural Science Foundation of China(32000969)the Key Support Program for Growth Factor Research(SZYZ-TR-03).
文摘Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).
基金supported by the National Natural Science Foundation of China (No. 81673858, No. 81704062, No. 30500644)the Science and Technology Project of Traditional Chinese Medicine in Hunan (No. 2009045, No. 2012027)the Program for National Center for Clinical Medicine for Geriatric Diseases (Ministry of Science and Technology)
文摘Background Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension(PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation and apoptosis balance. However, the molecular mechanism underlying of this balance is still unknown. Methods To clarify the biological effects of hypoxic air exposure and hypoxia-inducible factor-1α(HIF-1α) on pulmonary arterial smooth muscle cell(PASMC) and pulmonary arterial hypertension rats, the cells were cultured in a hypoxic chamber under oxygen concentrations. Cell viability, reactive oxygen species level, cell death, mitochondrial morphology, mitochondrial membrane potential, mitochondrial function and mitochondrial biosynthesis, as well as fission-and fusion-related proteins, were measured under hypoxic conditions. In addition, rats were maintained under hypoxic conditions, and the right ventricular systolic pressure, right ventricular hypertrophy index and right ventricular weight/body weight ratio were examined and recorded. Further, we assessed the role of HIF-1α in the development and progression of PH using HIF-1α gene knockdown using small interfering RNA transfection. Mdivi-1 treatment was performed before hypoxia to inhibit dynamin-related protein 1(Drp1). Results We found that HIF-1α expression was increased during hypoxia, which was crucial for hypoxia-induced mitochondrial dysfunction and hypoxia-stimulated PASMCs proliferation and apoptosis. We also found that targeting mitochondrial fission Drp1 by mitochondrial division inhibitor Mdivi-1 was effective in PH model rats. The results showed that mitochondrial dynamics were involved in the pulmonary vascular remodeling under hypoxia in vivo and in vitro. Furthermore, HIF-1α also modulated mitochondrial dynamics in pulmonary vascular remodeling under hypoxia through directly regulating the expression of Drp1. Conclusions In conclusion, our data suggests that abnormal mitochondrial dynamics could be a marker for the early diagnosis of PH and monitoring disease progression. Further research is needed to study the signaling pathways that govern mitochondrial fission/fusion in PH.
基金The project supported by the National Nature Science Foundation of China (No. 19890300)
文摘From a population of about 3500 single plants in Arabidopsis promoter trapping bank, one plant whose GUS-gene had been specifically expressed in vascular bundle, was screened by the method of gus tissue staining. The T-DNA flanking sequence was amplified using TAIL-PCR. This band will be purified and connected to TA cloning vector. After sequencing and searching in the genebank, its function will be demonatrated through transformation.
文摘BACKGROUND: This study aims to evaluate the results of studies investigating neutrophilto-lymphocyte ratio(NLR) and to identify the prognostic and diagnostic value of NLR in occlusive vascular diseases.METHODS: With the aim of identifying the studies related to NLR, a search was performed on http://www.ncbi.nlm.nih.gov/pubmed by using the key words "neutrophil lymphocyte ratio" between January 2005 and December 2014. All of the original articles were evaluated according to date of publications, countries, clinics and topics. Studies about occlusive vascular diseases were evaluated according to their qualifications, review methods and results. SPSS for Windows 16.0 was used in data analysis and data were expressed as mean, standard deviation and percentage.RESULTS: A total of 735 original research articles were investigated. The number of publications have shown a regular logarithmic increase over the years. Thirty-two percent of all publications were performed by clinics in Turkey and 56.4% were performed by general-oncological surgery and cardiology clinics. A total of 107 publications were identified to be about occlusive vascular diseases, 80.3% of these publications were found to be prognostic and 19.6% to be diagnostic, 82.2% of them were found to be planned as retrospective and 17.7% as prospective. In 95.3% of prognostic publications, there was a positive correlation between high NLR values at admission and poor prognosis. In 95.3% of diagnostic publications high NLR values at admission were identifi ed to be signifi cant diagnostically.CONCLUSION: Elevated neutrophil-to-lymphocyte ratio at admission, could be used as a diagnostic and/or prognostic parameter in occlusive vascular diseases.
文摘Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.
基金supported by grants from the National Natural Science Foundation of China(81773931 and 81374004)the Beijing Municipal Administration of Hospitals’Youth Program(QML20170105)+1 种基金the Natural Science Foundation of Beijing Municipality(7173253)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support“Yangfan”Project(ZYLX201802)。
文摘BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.
基金supported by the National Natural Science Foundation of China(grant number 81570441)the Program for Changjiang Scholars and the Innovative Research Team in the University(IRT1216)
文摘Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS), and has become one of the most important causes of death for intensive care units(ICU) patients. Currently, although there has been some progress in knowledge of the pathogenesis of these vascular disorders, the detailed mechanisms remain unclear, and effective prophylaxis and treatment are still lacking. In this study, we aimed to provide a review of the literature regarding the regulatory mechanisms and prophylaxis as well as the treatment of vascular leakage in critical diseases such as severe trauma and shock, which could be beneficial for the overall clinical treatment of vascular leakage disorders.
基金supported by grants from the National Key Research and Development Program of China (2020YFA0908200)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20171906)+2 种基金Shanghai Municipal Health and Family Planning Commission (2022XD055)Natural Science Foundation of Shandong Province (Shandong) (ZR2020QH121)GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine
文摘Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.
基金ThisstudywassupportedinpartbythemedicalresearchgrantsofGuangdongProvince (No :A19990 48)
文摘Objective. To determine whether serum vascular endothelial growth factor(VEGF)concentrations are altered in several kinds of coronary heart disease patients. Materials and methods. Using a VEGF enzyme-linked immunosorbent assay(ELISA), serum VEGF concentrations were determined in antecubital venous blood of 16 patients with stable angina pectoris(SAP), 16 with unstable angina pectoris(UAP) and 16 with acute myocardial infarction(AMI) before and after thrombolytic therapy, and of 16 age- and sex-matched healthy volunteers who used as controls. Results. The concentrations of serum VEGF in patients with SAP(9860±2699pg/ml) and UAP (10361±2489pg/ml) tended to be higher than those in control subjects(8044±2457pg/ml), but the differences did not reach statistical significance (P>005 for each). Before thrombolytic therapy, the concentrations of serum VEGF in patients with AMI (28592±12515pg/ml) were significantly higher than those in patients with SAP, UAP or control subjects (P<001,respectively), and correlated with synchronous serum creatine kinase (CK) and its MB isoenzyme (CK-MB) contents(r=0866,P<0001 and r=0948,P<0001;respectively). Three hours after thrombolysis, the concentrations of VEGF had fallen to 11157±3129pg/ml (P<001 vs. before thrombolytic therapy and P<005 vs.control subjects). Conclusion. The present study shows that serum concentrations of VEGF in patients with AMI are markedly elevated and that increased serum VEGF levels may be one of the most sensitive indexes in diagnosing AMI and judging reperfusion.
基金This project was supported by Grant 31200884 from the National Natural Science Foundation of China Grant 2016D016, 2016-ZQN-92, and 2016-2-75 from the Natural Science Foundation of Fujian and Grant 3502Z20154048, 3502Z20144061, and 3502Z20154047 from the Natural Scien- ce Foundation of Xiamen.
文摘Background In type 2 diabetes mellitus （T2DM）, high-density lipoprotein （HDL） impairs its anti-atherogenic properties and even develops to a pro-inflammatory and pro-atherogenic phenotype because of abnormal compositions and modifications. In this study, we ex- amined the effects and the related mechanisms of glycation of HDL on the proliferation and migration of vascular smooth muscle cells （VSMCs）. Methods ＆ Results Glycated HDL （G-HDL） was modified with D-glucose （25 mmol/L） in vitro. Diabetic HDL （D-HDL） was isolated from T2DM patients. Rat VSMCs were isolated from the thoracic aortas. Human VSMCs were obtained from ScienCell Research Laboratories. Alpha-actin was detected through immunofiuorescence. VSMC proliferation was assayed by Cell Count. VSMC migration was determined by transwell chamber and scratch-wound assay. Intracellular reactive oxygen species （ROS） was detected based on ROS-medi- ated 2＇,7＇-dichlorofluorescein （DCFH-DA） fluorescence. Compared to native HDL （N-HDL）, G-HDL remarkably promoted VSMC prolif- eration and migration in the dose and time-dependent manners. In addition, G-HDL enhanced ROS generation in VSMCs. However, the ROS scavenger, N-acetylcysteine, efficiently decreased ROS production and subsequently inhibited the proliferation of VSMCs induced by G-HDL. Similarly, D-HDL from T2DM patients also promoted ROS release and VSMC proliferation and migration. Conclusions HDL either glycated in vitro or isolated from T2DM patients triggered VSMC proliferation, migration, and oxidative stress. These results might partly interpret the higher morbidity of cardiovascular disease in T2DM patients.
文摘Efficient strategies to promote microvascularization in vascular tissue engineering,a central priority in regenerative medicine,are still scarce;nano-and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering.Capillaries are the smallest type and in numerous blood vessels,which are distributed densely in cardiovascular system.To mimic this microvascular network,specific cell components and proangiogenic factors are required.Herein,advanced biofabrication methods in microvascular engineering,including extrusion-based and droplet-based bioprinting,Kenzan,and biogripper approaches,are deliberated with emphasis on the newest works in prevascular nano-and micro-sized aggregates and microspheres/microbeads.
文摘BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.METHODS： A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly： a control group （S group, n=32） and a MSCs treatment group （M group, n=32）. 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 （baseline）, 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.RESULTS： In the lung tissue, VEGF decreased gradually in the S group （P〈0.05） and signi？ cantly decreased in the M group （P〈0.05）, but it increased more signi？ cantly than the values at the corresponding time points （P〈0.05）. In peripheral blood, VEGF increased gradually in the S group （P〈0.05） and markedly increased in the M group （P〈0.05）, but it decreased more signi？ cantly than the values at corresponding time points （P〈0.05）.CONCLUSION： MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.
文摘To investigate the dynamic changes of serum vascular endothelial growth factor(VEGF) levels in a rat model of acute myocardial infarction. Materials and methods.Eighty eight adult male Sprague Dawley rats weighing approximately 270 g were used in this study. Eighty rats were subjected to left coronary artery ligation, with 8 rats for each different duration of infarct. Eight sham operated animals in which the left coronary artery was surgically exposed without ligation were used as controls. Blood samples were drawn from the right atrium before (sham animals) and 1,3,6,12,24 h and 2,3,5,7,14 d after myocardial infarction. The concentrations of serum VEGF were measured by a sensitive enzyme linked immunosorbent assay with a rabbit polyclonal antibody specific for VEGF. Results. In the 8 control animals, the mean concentration of serum VEGF was 66.99±17.83 pg/ml. Six hours after myocardial infarction, the level of serum VEGF significantly increased to 125.68±28.07 pg/ml (P<0.01 vs. sham controls), and reached a peak (240.61±70.63 pg/ml. P<0.01 vs. sham animals) at 24 h after ligation and then decreased gradually over the remaining 2 weeks. However, the level remained significantly elevated for 14 d (107.64±30.13pg/ml, P<0.01 vs. sham controls). Conclusion. The present study shows that the levels of serum VEGF are markedly increased until 14 d in the rat model of acute myocardial infarction. The increased serum VEGF level may play an important role in the angiogenesis associated with myocardial infarction.
基金Supported by the National Natural Science Foundation of China(81270399and81100226)
文摘Objective To construct the zinc finger protein-activating transcription factor (ZFP-ATF) plasmid and evaluate its efficacy in inducing vascular endothelial growth factor (VEGF) expression in EY.HY926 endothelial cells. Methods Firstly, we constructed the ZFP-ATF plasmid, then testified the quantity of VEGF protein in EY.HY926 endothelial cells after transfected with ZFP-ATP plasmid by Western blot, finally, we used the RT-PCR to testify whether the ZFP-ATF can stimulate expression of VEGF splice variants. Results The ZFP-ATF DNA sequences were located the multiclone sites of PVAX1 vector between the site of BamH Ⅰ and Xhol. Western blot result showed VEGF expression in EY.HY926 endothelial cells transfected with ZFP-ATF plasmid was significantly higher than that in cells transfected with VEGF165 (19.95±3.95 vs. 12.15±1.55 μg/μL, P<0.01). RT-PCR result showed VEGF-A mRNA expression level induced by ZFP-ATF was high than that induced by VEGF165. Conclusion ZFP-ATF can up-regulate the VEGF-A expression in comparison with VEGF165, which might have beneficial effects in angiogenesis process.
基金Supported by the National Natural Science Foundation of China(81102444)Special Fund of the National Laboratory of China(2060204)
文摘Objective To study the role of sirtuin 1 （SIRT1） in Fas ligand （FasL） expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell （VSMC） lysate. Smooth muscle cell （SMC）-specific human SIRT1 transgenic （Tg） C57BL/6 mice and their littermate wild-type （WT） controls underwent complete carotid artery ligation （ligation groups） or the ligation-excluded operation （sham groups）. The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 （SIRT1H363Y）, and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation （P〈0.001） and VSMCs treated with serum （P〈0.05 at the transcriptional level, P〈0.001 at the protein level）. No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL （P〈0.001）. The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 （P〈0.001）, while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 （P〈0.001）. Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.
文摘To observe the regulating effects of vascular endothelial growth factor (VEGF) and angiotensinⅡ (ANG II) on the frog’s pericardium, lymphatic stomata and angiogenesis so as to reveal their effects and mechanism on the mesothelial permeability, lymphatic stoma regulation and myocardial hypertrophy. Methods. VEGF and ANGⅡ were injected into the frog’s peritoneal cavity so as to examine the changes of the pericardial stromata by using transmission electron microscopy, scanning electron microscopy and computerized imaging analysis. Results. Scattered distributed pericardial stomata were found on the parietal pericardium of the frog with a few sinusoid mesothelial cells, whose blood supply was directly from the cardiac chambers flowing into the trabecular spaces of the myocardium (because there are no blood vessels in the myocardium of the frog). The average diameters of the pericardial stomata in VEGF and ANGⅡ groups were 1.50μ m and 1.79μ m respectively, which were much larger than those in the control group (0.72μ m, P Conclusions. VEGF and ANGⅡ could strongly regulate the pericardial stomata by increasing their numbers and openings with larger diameters and higher distribution density. They could also increase the sinusoid areas with the result of the higher permeability of the pericardium, which clearly indicated that VEGF and ANGⅡ could speed up the material transfer of the pericardial cavity and play an important role in preventing myocardial interstitial edema. Yet there was no strong evidence to show the angiogenesis in the myocardium.
文摘Diepithelialized tissue flap(DTF)with vascular anastomosis was de-signed in August 1987,and was used for the repair of 12 cases of large intraoraltissue defect.All the operations were successful.The clinical data were reportedand the procedure to incise and transplant a DTF described.When the healingprocess and changes of DTF after transplantation were observed,it was foundthat a layer of new smooth epidermis was formed on the surface of the DTF.Theorigin of this new epidermis was discussed.Ten out of the 12 cases have been fol-lowed up for from half a year to 2 and a half years,and the results weresatisfactory.The new epidermis showed no hair growth and the patients did nothave any rough feeling,which usually occurred after ordinary skin grafting.It isbelieved that DTF transplantation is likely an ideal method for the repair andreconstruction of intraoral soft tissue defect.Its disadvantage was that the DTFcontracted severely after healing.Finally the authors put forward the problemsconcerning the transplantation of DTF,which should be investigated further.
