Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive...Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.展开更多
Hypoxia and endothelin-1 (ET-1) are associated with constriction of pulmonary vasculature both in vivo and in vitro. However, the role of hypoxia and ET-1 in the vascular remodelling during the development of pulmonar...Hypoxia and endothelin-1 (ET-1) are associated with constriction of pulmonary vasculature both in vivo and in vitro. However, the role of hypoxia and ET-1 in the vascular remodelling during the development of pulmonary hypertension is unclear. This study demonstrated that ET-1(0. 1 nmol/L to 100 nmol/L) increased the [￣3H]thymidine uptake in a dose-dependent manner in cultured bovine pulmonary artery smooth muscle cells(PASMC). which was enhanced by exposing PASMC to hypoxia (2%O2, 93%N2,5%CO2 ). BQ123, the specific antagonist of endothelin receptor subtype A,eliminated the ET-1 medicated proliferation of PASMC and the cooperative effect of hypoxia. Some dilatory drugs could inhibite the mitogenic effect of ET-1. We also observed that hypoxia significantly increased [￣3H] thymidine uptake in PASMC without ET-1 and BQ123 could inhibite this effect. Radioimmunoassay suggested that there was an autocrine of ET-1 in cultured PASMC which was enhanced by hypoxia significantly.展开更多
The responses of choriocapillary endothelial cells(CCE) and retinal capillary endothelial cells(RCE) in culture,in terms of phosphoinositide(PI) breakdown and cellular mitogenesis, to retinal pigment epithelial cell(R...The responses of choriocapillary endothelial cells(CCE) and retinal capillary endothelial cells(RCE) in culture,in terms of phosphoinositide(PI) breakdown and cellular mitogenesis, to retinal pigment epithelial cell(RPE)-conditioned medium and vasoactive agents have been compared. RPE-conditioned medium did not induce PI breakdown in either type of cell. However, it stimulated DNA synthesis in CCE but not in RCE. Bradykinin(BDK) acted as both a fast signaling and a slow mitogenic factor on CCE, but BDK did not affect PI turnover or DNA synthesis in RCE. In contrast, thrombin stimulated PI turnover in RCE but not in CCE, though it did not induce 3H-thymidine incorporation into either type of cell. These differences in cellular functions between CCE and RCE following stimulation suggest that induction of DNA synthesis and receptor-mediated PI turnover by external factors is determined, at least in part, by the origin of the capillary endothelial cell. Therefore, extrapolation to CCE pathophysiology from experiments using endothelial cells from other capillary origins may not be valid.展开更多
Objective： To explore the mechanism of native Tibetan fetuses adaptation to hypoxia, we tried to find the different expression genes about mitochondrial function in the native Tibetan placents. Methods： In this stud...Objective： To explore the mechanism of native Tibetan fetuses adaptation to hypoxia, we tried to find the different expression genes about mitochondrial function in the native Tibetan placents. Methods： In this study, the placents of native Tibetan and the high-altitude Hart （ha-Hart） were collected. After the total RNA extraction, the finally synthesized cDNAs were hybridized to mitochondrial array to find the altered expression genes between them. Then, the cytochrome c oxidase 17 （Coxl7）, dynactin 2 （DCTN2, also known as p50）, and vascular endothelial growth factor receptor （VEGFR, also known as KDR） were chosen from the altered expression genes to further verify the array results using the SYBR Green real-time PCR. Because the altered expression genes （such as Cybb and Cox 17） in the array results related to the activities of COXI and COXIV, the placental mitochondria activities of COXI and COXIV were measured to find their changes in the hypoxia. Results： By a standard of≥1.5 or ≤0.67, there were 24 different expressed genes between the native Tibetan and the ha-Han placents, including 3 up-regulated genes and 21 down-regulated genes. These genes were related to energy metabolism, signal transduction, cell proliferation, electron transport, cell adhesion, nucleotide-excision repair. The array results of Cox17, DCTN2 and KDR were further verified by the real-time RT-PCR. Through the mitochondria respiration measurements, the activity of COXI in the native Tibetan placents were higher than that of ha-Han, there was no difference in COXIV activity between them. Conclusion： The altered mitochondrial related genes in the native Tibetan placents may have a role in the high altitude adaptation for fetuses through changing the activity of mitochondrial COX.展开更多
Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin...Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wntl and dickkopf-related protein-1 （DKK1）. Methods The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wntt and nuclear factor-r,B （NF-κB） were measured with RT-PCR and Westem Blot. Serum levels of interleukin-12 （IL-12） were quantified with ELISA. Results The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wntl and decreased DKKI expression and elevated the ratio of Wntl/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide monoor combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial ceils stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wntl and decreased DKK1 expression and elevated the ratio of Wntl/DKK1. Condusions Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wntl and inhibit- ing DKK1 expression.展开更多
基金Supported by Sciences and Technology Commission of Shanghai Municipality (08ZR1422100 and 08410701200)
文摘Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.
文摘Hypoxia and endothelin-1 (ET-1) are associated with constriction of pulmonary vasculature both in vivo and in vitro. However, the role of hypoxia and ET-1 in the vascular remodelling during the development of pulmonary hypertension is unclear. This study demonstrated that ET-1(0. 1 nmol/L to 100 nmol/L) increased the [￣3H]thymidine uptake in a dose-dependent manner in cultured bovine pulmonary artery smooth muscle cells(PASMC). which was enhanced by exposing PASMC to hypoxia (2%O2, 93%N2,5%CO2 ). BQ123, the specific antagonist of endothelin receptor subtype A,eliminated the ET-1 medicated proliferation of PASMC and the cooperative effect of hypoxia. Some dilatory drugs could inhibite the mitogenic effect of ET-1. We also observed that hypoxia significantly increased [￣3H] thymidine uptake in PASMC without ET-1 and BQ123 could inhibite this effect. Radioimmunoassay suggested that there was an autocrine of ET-1 in cultured PASMC which was enhanced by hypoxia significantly.
文摘The responses of choriocapillary endothelial cells(CCE) and retinal capillary endothelial cells(RCE) in culture,in terms of phosphoinositide(PI) breakdown and cellular mitogenesis, to retinal pigment epithelial cell(RPE)-conditioned medium and vasoactive agents have been compared. RPE-conditioned medium did not induce PI breakdown in either type of cell. However, it stimulated DNA synthesis in CCE but not in RCE. Bradykinin(BDK) acted as both a fast signaling and a slow mitogenic factor on CCE, but BDK did not affect PI turnover or DNA synthesis in RCE. In contrast, thrombin stimulated PI turnover in RCE but not in CCE, though it did not induce 3H-thymidine incorporation into either type of cell. These differences in cellular functions between CCE and RCE following stimulation suggest that induction of DNA synthesis and receptor-mediated PI turnover by external factors is determined, at least in part, by the origin of the capillary endothelial cell. Therefore, extrapolation to CCE pathophysiology from experiments using endothelial cells from other capillary origins may not be valid.
基金Supported by the National Basic Research Program of China (973 Program, 2006CB504101)the National Natural Science Foundation of China (30393131)
文摘Objective： To explore the mechanism of native Tibetan fetuses adaptation to hypoxia, we tried to find the different expression genes about mitochondrial function in the native Tibetan placents. Methods： In this study, the placents of native Tibetan and the high-altitude Hart （ha-Hart） were collected. After the total RNA extraction, the finally synthesized cDNAs were hybridized to mitochondrial array to find the altered expression genes between them. Then, the cytochrome c oxidase 17 （Coxl7）, dynactin 2 （DCTN2, also known as p50）, and vascular endothelial growth factor receptor （VEGFR, also known as KDR） were chosen from the altered expression genes to further verify the array results using the SYBR Green real-time PCR. Because the altered expression genes （such as Cybb and Cox 17） in the array results related to the activities of COXI and COXIV, the placental mitochondria activities of COXI and COXIV were measured to find their changes in the hypoxia. Results： By a standard of≥1.5 or ≤0.67, there were 24 different expressed genes between the native Tibetan and the ha-Han placents, including 3 up-regulated genes and 21 down-regulated genes. These genes were related to energy metabolism, signal transduction, cell proliferation, electron transport, cell adhesion, nucleotide-excision repair. The array results of Cox17, DCTN2 and KDR were further verified by the real-time RT-PCR. Through the mitochondria respiration measurements, the activity of COXI in the native Tibetan placents were higher than that of ha-Han, there was no difference in COXIV activity between them. Conclusion： The altered mitochondrial related genes in the native Tibetan placents may have a role in the high altitude adaptation for fetuses through changing the activity of mitochondrial COX.
基金This study was funded by grants from the Natural Science Foundation of Hubei Province in China （2012FFB02508）.
文摘Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wntl and dickkopf-related protein-1 （DKK1）. Methods The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wntt and nuclear factor-r,B （NF-κB） were measured with RT-PCR and Westem Blot. Serum levels of interleukin-12 （IL-12） were quantified with ELISA. Results The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wntl and decreased DKKI expression and elevated the ratio of Wntl/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide monoor combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial ceils stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wntl and decreased DKK1 expression and elevated the ratio of Wntl/DKK1. Condusions Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wntl and inhibit- ing DKK1 expression.
