PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.
PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.
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PEDF 通过抑制血管通透性和心肌细胞凋亡改善急性心肌梗死大鼠的心脏功能
DOI：
10.3390/ijms16035618
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发表时间：
2015-03-11
影响因子：
5.6
通讯作者：
Dong HY
中科院分区：
文献类型：
--
作者：
Zhang H;Wang Z;Feng SJ;Xu L;Shi HX;Chen LL;Yuan GD;Yan W;Zhuang W;Zhang YQ;Zhang ZM;Dong HY
色素上皮源性因子(PEDF)是一种多效性基因，具有抗炎、抗氧化和抗血管生成等特性。然而，最近关于PEDF对心肌细胞的影响的报道存在争议，目前尚不清楚PEDF是否以及如何抑制心脏缺氧或缺血的内皮损伤。本研究建立了成年SD大鼠急性心肌梗死(AMI)模型。将PEDF-小干扰RNA(SiRNA)-慢病毒(PEDF-RNAi-LV)或PEDF-LV分别沿梗死区边缘注入心肌，以下调或过表达PEDF。分析血管通透性、心肌细胞凋亡率、心肌梗死面积和动物心功能。此外，我们还观察了PEDF在体外对缺氧状态下内皮细胞通透性和心肌细胞凋亡的抑制作用。结果表明，PEDF可显著抑制缺氧诱导的血管通透性，并通过PPARγ依赖的紧密连接(TJ)的产生抑制内皮通透性。PEDF通过抑制caspase-3的激活，在体内和体外保护心肌细胞免受缺血或缺氧诱导的细胞凋亡。我们还发现，PEDF显著缩小了急性心肌梗死大鼠的心肌梗死范围，并增强了心功能。这些数据表明，PEDF至少通过减少血管通透性、心肌细胞凋亡和心肌梗死范围来保护心脏功能免受缺血损伤。
Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF’s effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.
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影响因子：
10.8
作者：
Maczewski, Michal;Mackiewicz, Urszula
通讯作者：
Mackiewicz, Urszula
DOI：
10.1016/j.bbrc.2004.10.041
发表时间：
2004-12-10
影响因子：
3.1
作者：
Sawant, S;Aparicio, S;Tombran-Tink, J
通讯作者：
Tombran-Tink, J
人骨髓间充质干细胞来源的细胞外囊泡促进大鼠心肌梗死模型中的血管生成
影响因子：
4.7
作者：
Bian, Suyan;Zhang, Liping;Yu, Hepeng
通讯作者：
Yu, Hepeng
影响因子：
4.8
作者：
Subramanian, Preeti;Locatelli-Hoops, Silvia;Becerra, S. Patricia
通讯作者：
Becerra, S. Patricia
影响因子：
15.9
作者：
Wencker, D;Chandra, M;Kitsis, RN
通讯作者：
Kitsis, RN