1 Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, P.R. China.
2 Morphological Research Experiment Center, Xuzhou Medical University, Xuzhou, P.R. China.
Hum Gene Ther. 2019 Jun;30(6):762-776. doi: 10.1089/hum.2018.186. Epub 2019 Mar 29.
The failure to maintain the viability of ischemic myocardium is one of the mechanisms that causes ischemic heart dysfunction after revascularization. Hibernating myocardium is considered to be able to maintain long-term viability during chronic hypoperfusion. Pigment epithelium-derived factor (PEDF) decreases the contractility of hypoxic cardiomyocytes and protects cardiomyocytes against ischemic injury, which is strikingly similar to the pathophysiologic characteristics of hibernating myocardium. It was therefore postulated that PEDF may induce acute ischemic myocardium into a "hibernating-like" state to maintain its viability. Adult Sprague-Dawley rat models of acute myocardial infarction were surgically established. Lentiviral vectors carrying the (PEDF-LVs) were delivered into myocardium with infarction to overexpress PEDF locally. It was found that PEDF local overexpression significantly reduced myocardial infarct size and cardiomyocytes necrosis but did not improve cardiac function at rest. The contractile reserve assessed by low-dose dobutamine stress echocardiography and "perfusion-metabolism mismatch" assessed by positron emission tomography, which are the characteristics of viable myocardium in hibernation, were observed in the PEDF overexpressed ischemic heart. Ultrastructural changes observed by electron microscopy and glycogen deposition explored by Periodic acid-Schiff staining were similar to the histological characteristics of hibernating myocardium. Moreover, PEDF overexpression protected the cardiomyocytes against anoxic injury and retained their functional recovery potential after reoxygenation . PEDF local overexpression may induce acute ischemic myocardium into a "hibernating-like" state and maintain its viability. This novel effect of PEDF presents an important clinical approach to enhance functional recovery after revascularization therapy in acute myocardial infarction.
缺血心肌的活力丧失是血运重建后缺血性心脏功能障碍的机制之一。冬眠心肌被认为在慢性低灌注期间能够保持长期活力。色素上皮衍生因子 (PEDF) 降低缺氧心肌细胞的收缩力并保护心肌细胞免受缺血性损伤，这与冬眠心肌的病理生理特征非常相似。因此，有人推测 PEDF 可能使急性缺血心肌进入“冬眠样”状态以维持其活力。通过手术建立了急性心肌梗死的成年 Sprague-Dawley 大鼠模型。携带 PEDF 的慢病毒载体 (PEDF-LVs) 被递送到梗塞心肌中以局部过表达 PEDF。结果发现，PEDF 局部过表达显著减少心肌梗死面积和心肌细胞坏死，但不能改善静息时的心脏功能。通过低剂量多巴酚丁胺超声心动图评估的收缩储备和正电子发射断层扫描评估的“灌注-代谢不匹配”，这是冬眠心肌中存活心肌的特征，在过表达 PEDF 的缺血心脏中观察到。电镜观察到的超微结构变化和过碘酸希夫染色探索到的糖原沉积与冬眠心肌的组织学特征相似。此外，PEDF 过表达可保护心肌细胞免受缺氧损伤，并在再氧合后保留其功能恢复潜力。PEDF 局部过表达可能使急性缺血心肌进入“冬眠样”状态并维持其活力。PEDF 的这种新作用为增强急性心肌梗死后血运重建治疗后的功能恢复提供了一种重要的临床方法。
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