Date Published: January 13, 2020
Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Author(s): Zhou Bin, Yu Yanli, Qiu Zhen, Meng Qingtao, Xia Zhongyuan.
To investigate whether GDF11 ameliorates myocardial ischemia reperfusion (MIR) injury in diabetic rats and explore the underlying mechanisms.
Diabetic and non-diabetic rats subjected to MIR (30 min of coronary artery occlusion followed by 120 min of reperfusion) with/without GDF11 pretreatment. Cardiac function, myocardial infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) 15-F2tisoprostane, autophagosome, LC3II/I ratio and Belcin-1 level were determined to reflect myocardial injury, oxidative stress and autophagy, respectively. In in vitro study, H9c2 cells cultured in high glucose (HG, 30mM) suffered hypoxia reoxygenation (HR) with/without GDF11, hydrogen peroxide (H2O2) and autophagy inhibitor 3-methyladenine (3-MA) treatment, cell injury; oxidative stress and autophagy were assessed.
Pretreatment with GDF11 significantly improved cardiac morphology and function in diabetes, concomitant with decreased arrhythmia severity, infarct size, CK-MB, LDH and 15-F2tisoprostane release, increased SOD activity and autophagy level. In addition, GDF11 notably reduced HR injury in H9c2 cells with HG exposure, accompanied by oxidative stress reduction and autophagy up-regulation. However, those effects were completely reversed by H2O2 and 3-MA.
GDF11 can provide protection against MIR injury in diabetic rats, and is implicated in antioxidant stress and autophagy up-regulation.
The incidence of diabetes has increased rapidly in recent decades; the latest data from the International Diabetes Federation showed that the number of adult diabetic patients worldwide is more than 415 million. It has become a global public health problem, endangering human health and increasing social burden. Recent evidence-based on medical studies demonstrated that ischemic heart disease remains a major cardiovascular complication and the leading cause of death in diabetic patients1,2. Patients with diabetes are more vulnerable to myocardial ischemia reperfusion (MIR) injury, and the risk of post-myocardial infarction death is 2~4 times higher than that of non-diabetic individuals3. The pathophysiologic mechanisms of MIR in diabetes are complicated; this fact has increased awareness and has been deeply explored.
The experimental protocols were in accordance with the principles of Animal Care of Wuhan University (Wuhan, China), and approved by the Committee for the Use of Live Animals in Teaching and Research.
The present study demonstrated that exogenous GDF11 provides cardioprotective effects against MIR in STZ-induced type 1 diabetic rats. Our results indicated that pretreatment with GDF11 remarkably improved cardiac function and reduced post-ischemia myocardial infarct size, which may be implicated in antioxidant stress and up-regulating autophagy level in diabetic myocardium. To the best of our knowledge, this is the first study to investigate the effects of GDF11 on IR injury in diabetic myocardium and hyperglycemic cardiomyocytes, and to explore the roles of oxidative stress and autophagy in this process.
GDF11 contributes to morphologic and functional recovery after MIR injury in diabetic rats, and may be implicated in antioxidant stress and up-regulation autophagy during IR injury.