To investigate the relationships between the expressions of p15,p16 and vascular endothelial growth factor (VEGF) and gastric carcinoma(GC). Methods: Using Immunohistochemical staining to examine the expressions of p1...To investigate the relationships between the expressions of p15,p16 and vascular endothelial growth factor (VEGF) and gastric carcinoma(GC). Methods: Using Immunohistochemical staining to examine the expressions of p15, p16 and VEGF In archival wax-embedded specimens of 80 GC and 20 gastric benign disease (GBD). Results: The positive expression rate (PER) of p15 was significantly lower in GC than in GBD (43.75% VS. 69.23%, P<0.05). No relationship was found between PER of p15 and clinicopathologic factors. PER of p16 was 20% in GC, 55% in GBD (P<0.01). PER of p16 wasn't significantly different in gross types, histological types, with or without distant metastasis and pTNM stages. PER of p16 was 71.43% in invasive mucosa or submucosa group, 17.24% in invasive muscle group and 13.64% in invasive serosa group (P<0.01); 12.96% in GC with lymph nodes metastasis, 34.62% in GC without lymph node metastasis (P<0.05). PER of VEGF in GC was 75.00%, in GBD 7.69% (P<0.001), in ul-cerative type of GC and infiltrating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
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
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
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
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
Objective: To explore the role of vascular endothelial growth factor (VEGF) in the angiogenesis and development of human gastric carcinoma. Methods: The expressions of VEGF and its receptor KDR (ki-nase-domain insert ...Objective: To explore the role of vascular endothelial growth factor (VEGF) in the angiogenesis and development of human gastric carcinoma. Methods: The expressions of VEGF and its receptor KDR (ki-nase-domain insert containing receptor) in human gastric cancer tissue and SGC-7901 cells were detected with immunohistochemical staining. Microvessel density (MVD) was obtained after immunostaining for Factor-VIII. VEGF in SGC-7901 cell line was detected with Western blot. VEGF levels were manipulated in human gastric cancer cell by using eukaryotic expression vector containing the complete VEGF165 complimentary DNA in either the sense or antisense orientation. Finally the biological characteristics of the transfectants were identified. Results: VEGF-positive rate in TNM grade I and IV gastric carcinomas (19. 0%) were significantly higher than that in grade I and I (72. 4%) (P<0. 05). Increased MVD was found in VEGF-positive tumors (16. 4±6. 7). which is significantly larger than in VEGF-negative tumors (6. 5±2. 1) (P< 0. 05). Human gastric cancer cells (SGC-7901) produced 3 kinds of VEGF in molecule. In 2 cases of 50 specimens, a few gastric cancer cells expressed KDR in cytoplasm and cell membranes. SGC-7901 cells with anti-sense VEGF165 showed a significant reduction in cell surface VEGF protein with the immunofluorescence intensity from 8. 9% to 31. 6% (P<0. 05). However, those with stable integration of VEGF165 in the sense orientation resulted in an increase in cellular and cell surface VEGF with the immunofluorescence intensity from 75. 4% to 31. 6% (P<0. 05). The decrease of VEGF levels was associated with a marked decrease in the growth of nude mouse xenografted tumor (33 d post-implantation, 345. 4±136. 3 mm3 in size) (P<0. 05 vs control SGC-7901 group) , whereas VEGF overexpression resulted in an increase of xenografted tumor size (33 d post-implantation, 2 350. 5±637. 7 mm3 in size) (P<0. 05 vs control SGC-7901 group). Conclusion: VEGF plays an important role in the development of human gastric cancer, and might have an autocrine effect upon the gastric cancer cells. The inhibition of VEGF by antisense RNA expression might prevent solid tumor from growing and metastasizing.展开更多
Objective To investigate the effects of hepatocyte growth factor(HGF)on vascular endothelial cells apoptosis induced by advanced glycation end products(AGEs)and its possible mechanism. Methods Human umbilical vein end...Objective To investigate the effects of hepatocyte growth factor(HGF)on vascular endothelial cells apoptosis induced by advanced glycation end products(AGEs)and its possible mechanism. Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and intervened by different concentrations of AGEs and HGF.The cell inhibitory rates of each group with different culture time(12, 24, 48, and 72 hours)were measured by methyl thiazolyl tetrazolium(MTT)assay. The early stage apoptosis was detected by flow cytometry with Annexin V-FITC/PI double staining, morphology of cell apoptosis was observed by hoechst 33258 fluorescence staining, and the expression of apoptosis-associated genes Bax and Bcl-2 were determined by Western blotting.The activity of caspase-3 was detected by enzyme-linked immunosorbent assay (ELISA).Results Morphological observation indicated that high concentration of AGEs induced characteristic apoptotic changes in HUVECs.Within a certain concentration range, HUVECs apoptosis inducing rates by AGEs were in both dose- and time-dependent manners.HGF significantly inhibited the apoptosis of HUVECs induced by AGEs (P< 0.05).AGEs significantly promoted expression of Bax protein, but not Bcl-2.Whereas HGF significantly promoted the expression of Bcl-2(P<0.01)and decreased the activity of caspase-3(P<0.05)without affecting Bax level.Conclusions AGEs can induce the apoptosis of endothelial cells in vitro.HGF may effectively attenuate AGEs-induced endothelial cells apoptosis through upregulating Bcl-2 gene expression and inhibiting caspase-3 activation.展开更多
Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardia...Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.展开更多
文摘To investigate the relationships between the expressions of p15,p16 and vascular endothelial growth factor (VEGF) and gastric carcinoma(GC). Methods: Using Immunohistochemical staining to examine the expressions of p15, p16 and VEGF In archival wax-embedded specimens of 80 GC and 20 gastric benign disease (GBD). Results: The positive expression rate (PER) of p15 was significantly lower in GC than in GBD (43.75% VS. 69.23%, P<0.05). No relationship was found between PER of p15 and clinicopathologic factors. PER of p16 was 20% in GC, 55% in GBD (P<0.01). PER of p16 wasn't significantly different in gross types, histological types, with or without distant metastasis and pTNM stages. PER of p16 was 71.43% in invasive mucosa or submucosa group, 17.24% in invasive muscle group and 13.64% in invasive serosa group (P<0.01); 12.96% in GC with lymph nodes metastasis, 34.62% in GC without lymph node metastasis (P<0.05). PER of VEGF in GC was 75.00%, in GBD 7.69% (P<0.001), in ul-cerative type of GC and infiltrating
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.
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.
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.
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Objective: To explore the role of vascular endothelial growth factor (VEGF) in the angiogenesis and development of human gastric carcinoma. Methods: The expressions of VEGF and its receptor KDR (ki-nase-domain insert containing receptor) in human gastric cancer tissue and SGC-7901 cells were detected with immunohistochemical staining. Microvessel density (MVD) was obtained after immunostaining for Factor-VIII. VEGF in SGC-7901 cell line was detected with Western blot. VEGF levels were manipulated in human gastric cancer cell by using eukaryotic expression vector containing the complete VEGF165 complimentary DNA in either the sense or antisense orientation. Finally the biological characteristics of the transfectants were identified. Results: VEGF-positive rate in TNM grade I and IV gastric carcinomas (19. 0%) were significantly higher than that in grade I and I (72. 4%) (P<0. 05). Increased MVD was found in VEGF-positive tumors (16. 4±6. 7). which is significantly larger than in VEGF-negative tumors (6. 5±2. 1) (P< 0. 05). Human gastric cancer cells (SGC-7901) produced 3 kinds of VEGF in molecule. In 2 cases of 50 specimens, a few gastric cancer cells expressed KDR in cytoplasm and cell membranes. SGC-7901 cells with anti-sense VEGF165 showed a significant reduction in cell surface VEGF protein with the immunofluorescence intensity from 8. 9% to 31. 6% (P<0. 05). However, those with stable integration of VEGF165 in the sense orientation resulted in an increase in cellular and cell surface VEGF with the immunofluorescence intensity from 75. 4% to 31. 6% (P<0. 05). The decrease of VEGF levels was associated with a marked decrease in the growth of nude mouse xenografted tumor (33 d post-implantation, 345. 4±136. 3 mm3 in size) (P<0. 05 vs control SGC-7901 group) , whereas VEGF overexpression resulted in an increase of xenografted tumor size (33 d post-implantation, 2 350. 5±637. 7 mm3 in size) (P<0. 05 vs control SGC-7901 group). Conclusion: VEGF plays an important role in the development of human gastric cancer, and might have an autocrine effect upon the gastric cancer cells. The inhibition of VEGF by antisense RNA expression might prevent solid tumor from growing and metastasizing.
文摘Objective To investigate the effects of hepatocyte growth factor(HGF)on vascular endothelial cells apoptosis induced by advanced glycation end products(AGEs)and its possible mechanism. Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and intervened by different concentrations of AGEs and HGF.The cell inhibitory rates of each group with different culture time(12, 24, 48, and 72 hours)were measured by methyl thiazolyl tetrazolium(MTT)assay. The early stage apoptosis was detected by flow cytometry with Annexin V-FITC/PI double staining, morphology of cell apoptosis was observed by hoechst 33258 fluorescence staining, and the expression of apoptosis-associated genes Bax and Bcl-2 were determined by Western blotting.The activity of caspase-3 was detected by enzyme-linked immunosorbent assay (ELISA).Results Morphological observation indicated that high concentration of AGEs induced characteristic apoptotic changes in HUVECs.Within a certain concentration range, HUVECs apoptosis inducing rates by AGEs were in both dose- and time-dependent manners.HGF significantly inhibited the apoptosis of HUVECs induced by AGEs (P< 0.05).AGEs significantly promoted expression of Bax protein, but not Bcl-2.Whereas HGF significantly promoted the expression of Bcl-2(P<0.01)and decreased the activity of caspase-3(P<0.05)without affecting Bax level.Conclusions AGEs can induce the apoptosis of endothelial cells in vitro.HGF may effectively attenuate AGEs-induced endothelial cells apoptosis through upregulating Bcl-2 gene expression and inhibiting caspase-3 activation.
文摘Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.
