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.