Introduction
Coronary heart disease (CHD) is characterized by myocardial ischemia, anoxia and necrosis attributed to coronary atherosclerosis, which results in heart defects. CHD is a leading cause of death and disability, with a 10-year mortality rise of 60% in China[1, 2]. This devastating rise is mainly due to adverse trends in risk factors, such as blood pressure, cholesterol and diabetes[3]. Identifying mechanisms to inhibit myocardial cell apoptosis under a hypoxic-ischemic state is a recent topic of high interest in CHD research.
Many studies have shown that microRNAs (miRNAs), an abundant class of endogenic non-coding RNAs with approximately 22 nucleotides, are involved in a wide variety of biological processes by modulating the expression of target genes and pathways[4, 5]. For CHD, an increasing number of miRNAs have been identified that play considerable roles in CHD development, such as miR-320b[6], miR-224[7], miR-423, miR-208a and miR-1[8].
Among various miRNAs, miR-210 plays a significant role in the hypoxia response on the account of its high sensitivity to hypoxia. Recent evidence has emerged that suggests miR-210, as the main hypoxia-induced miRNA, has pivotal implications in cell survival and angiogenesis[9].. During hypoxia stress, miR-210 was potently upregulated in myocardial cells in vitro [10]. In addition, targeted miR-210 could effectively protect the heart from myocardial infarctions and promote functional recovery[11]. However, little is known about the mechanism of miR-210 in ischemia-hypoxia in myocardial cells.
Caspase-8-associated protein-2 (Caspase8ap2) consists of 1926 amino acids and is an integral member of the apoptosis signalling complex that activates caspase-8 and downstream caspase 3 by combining with the death receptor of procaspase-8[12]. Thus, Caspase8ap2 is considered a pro-apoptosis protein. Kim et al. reported that the apoptosis in mesenchymal stem cells (MSCs) caused by ischemic preconditioning (IP) was suppressed by miR-210 by repressing Caspase8ap2[12].
The present study was conducted to investigate the role of the miR-210/Caspase8ap2 pathway in apoptosis and autophagy in hypoxic myocardial cells. The findings of this study can potentially provide novel avenues for the treatment of myocardial injury induced by hypoxia.