Abstract
Recent studies have reported that miRNAs might play critical roles in acute myocardial infarction (AMI). The objective of this study is to investigate the role of miR-499-5p in AMI and its potential molecular mechanisms. The expression level of MiR-499-5p was remarkably decreased in the infarcted myocardial tissues and in the cultured neonatal rat cardiomyocytes induced by hypoxia. Overexpression or knockdown of miR-499-5p decreased or increased the apoptotic rates of cultured cardiomyocytes in vitro. In addition, ectopic overexpression of miR-499-5p in the rat AMI models with agomir reduced the myocardial infarct size through decreasing the cardiomyocytes apoptosis in the infarcted area of the rat hearts. PDCD4 (programmed cell death 4) was verified as a direct target of miR-499-5p by luciferase report assay, and ectopic overexpression or inhibition of miR-499-5p could inhibit or increase the PDCD4 expression at both the mRNA and protein levels. Furthermore, we found that ectopic overexpression of PDCD4 without miR-499-5p binding sites reversed miR-499-5p-mediated cardiomyocytes apoptosis. Together, these findings revealed the role of miR-499-5p in protecting the cardiomyocytes against apoptosis induced by AMI via its direct target PDCD4, which providing evidence for the miR-499-5p/PDCD4 pathway as a potential therapeutic target for patients with AMI.
Highlights
Acute myocardial infarction (AMI) is a common cardiovascular event and, the principal ischaemic episode is often not fatal, the damage to myocardial tissues that is caused by AMI can lead to the development of heart failure, even cardiogenic shock, or death [1]
MiR-499-5p inhibits cardiomyocytes apoptosis induced by hypoxia in vitro
The results displayed that miR499-5p mimics or inhibitor transfection could greatly inhibit or promote the cultured cardiomyocytes apoptosis induced by hypoxia compared with the control transfection (Figure 2C, p < 0.05)
Summary
Acute myocardial infarction (AMI) is a common cardiovascular event and, the principal ischaemic episode is often not fatal, the damage to myocardial tissues that is caused by AMI can lead to the development of heart failure, even cardiogenic shock, or death [1]. For these reasons, AMI is still a major global cause of morbidity and mortality, and approximately 3~4 million people each year are estimated to suffer from AMI. It was reported that the plasma level of miR499-5p was significantly increased in AMI rats [20]. The objective of this work is to study the role of miR-499-5p in AMI and its potential molecular mechanisms
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