Why the study?
Failure to maintain ischemic myocardial viability causes post-revascularization dysfunction, prompting investigation into whether PEDF can induce a hibernating-like state to preserve viability.
Does local PEDF overexpression reduce myocardial infarct size and maintain viability in rat models of acute myocardial infarction?
Does local PEDF overexpression reduce myocardial infarct size and maintain viability in rat models of acute myocardial infarction?
Local overexpression of PEDF in acute ischemic myocardium induces a 'hibernating-like' state that reduces infarct size and maintains myocardial viability in a rat model.
May guide PEDF gene therapy for ischemic viability; leaves open clinical translation pending validation.
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 gene (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 in vitro. 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.
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Yuan et al. (2019) studied this question.
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