Zhang Hao, Li Zhimin, Quan Xiaoyu, Liu Xiucheng, Sun Teng, Wei Tengteng, Pan Jiajun, Liu Zhiwei, Wang Meng, Dong Hongyan, Zhang Zhongming
Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Department of Cardiothoracic Surgery, Xuzhou Cancer Hospital, Xuzhou, China.
Hum Gene Ther. 2022 Mar;33(5-6):330-345. doi: 10.1089/hum.2021.068. Epub 2021 Aug 27.
The phenomenon of no-reflow seriously limits the therapeutic value of coronary recanalization and leads to poor prognosis. Recent studies have demonstrated the potential role of pigment epithelium-derived factor (PEDF) in stabilizing endothelial cell junction, reducing vascular permeability and maintaining a quiescent vasculature. In this study, intramyocardial gene delivery was performed 5 days before the acute myocardial infarction/recanalization experiment in male rats. Positron emission tomography perfusion imaging with N-NH indicated PEDF to promote microvascular reperfusion significantly 4 h postcoronary occlusion. PEDF was observed to maintain the stability of endothelial adherens junctions (AJs), thus preventing the occurrence of no-reflow. PEDF reduced the hypoxia-induced vascular endothelial (VE)-cadherin endocytosis through PEDF/LR/Src/VE-cadherin S665 axis , which was remarkably observed to maintain endothelial AJs. Generally, PEDF might function as a relevant target for therapeutic vasculoprotection by way of regulating the phosphorylation level of VE-cadherin according to our data, thus being crucial for preventing no-reflow.
无复流现象严重限制了冠状动脉再通的治疗价值，并导致预后不良。最近的研究表明，色素上皮衍生因子（PEDF）在稳定内皮细胞连接、降低血管通透性和维持血管静止方面具有潜在作用。在本研究中，在雄性大鼠急性心肌梗死/再通实验前5天进行心肌内基因递送。用N-NH进行的正电子发射断层扫描灌注成像表明，在冠状动脉闭塞后4小时，PEDF能显著促进微血管再灌注。观察到PEDF能维持内皮黏附连接（AJs）的稳定性，从而防止无复流的发生。PEDF通过PEDF/LR/Src/VE-钙黏蛋白S665轴减少缺氧诱导的血管内皮（VE）-钙黏蛋白内吞作用，这显著观察到能维持内皮AJs。一般来说，根据我们的数据，PEDF可能通过调节VE-钙黏蛋白的磷酸化水平作为治疗性血管保护的相关靶点，因此对预防无复流至关重要。
