Strategies to Attenuate Myocardial Infarction and No-Reflow Through Preservation of Vascular Integrity by Pigment Epithelium-Derived Factor.

Hao Zhang, Zhimin Li, Xiaoyu Quan, Xiucheng Liu, Teng Sun, Tengteng Wei, Jiajun Pan, Zhiwei Liu, Meng Wang, Hongyan Dong, Zhongming Zhang

Human gene therapy 2022 Mar

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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 13N-NH3 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 in vitro, 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.

Citation

Hao Zhang, Zhimin Li, Xiaoyu Quan, Xiucheng Liu, Teng Sun, Tengteng Wei, Jiajun Pan, Zhiwei Liu, Meng Wang, Hongyan Dong, Zhongming Zhang. Strategies to Attenuate Myocardial Infarction and No-Reflow Through Preservation of Vascular Integrity by Pigment Epithelium-Derived Factor. Human gene therapy. 2022 Mar;33(5-6):330-345