Abstract
Myocardial infarction (MI) is the most prevalent cardiac disease with high mortality, leading to severe heart injury. Circular RNAs (circRNAs) are a new type of regulatory RNAs and participate in multiple pathological cardiac progressions. However, the role of circRNAs Postn (circPostn) in MI modulation remains unclear. Here, we aimed to explore the effect of circPostn on MI-induced myocardial injury and cardiac remodeling. We identified that the expression of circPostn was elevated in the plasma of MI patients, MI mouse model, and hypoxia and reoxygenation (H/R)-treated human cardiomyocytes. The depletion of circPostn significantly attenuated MI-related myocardium injury and reduced the infarct size in MI mouse model. The circPostn knockdown obviously enhanced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) and inhibited left ventricular anterior wall thickness at diastole (LVAWd) and left ventricular posterior wall thickness at diastole (LVPWd). The depletion of circPostn was able to decrease MI-induced expression of collagen 1α1 and collagen 3α1 in the ventricular tissues of mice. The protein expression of collagen and α-smooth muscle actin (SMA) was up-regulated in MI mice and was inhibited by circPostn knockdown. Meanwhile, the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was repressed by circPostn depletion in the ventricular tissues of MI mice. Besides, the circPostn depletion attenuated cardiomyocyte apoptosis in mice. Mechanically, circPostn served as a miR-96-5p sponge and miR-96-5p-targeted BNIP3 in human cardiomyocytes, in which circPostn up-regulated BNIP3 expression by targeting miR-96-5p. circPostn promoted H/R-induced cardiomyocyte injury by modulating miR-96-5p/BNIP3 axis. Thus, we conclude that circPostn contributes to MI-induced myocardial injury and cardiac remodeling by regulating miR-96-5p/BNIP3 axis. Our finding provides new insight into the mechanism by which circPostn regulates MI-related cardiac dysfunction. circPostn, miR-96-5p, and BNIP3 are potential targets for the treatment of MI-caused heart injury.
Highlights
Coronary heart disease is featured by the formation of stable atheromas that induce chronic myocardial ischemia or vulnerable plaques that lead to acute occlusive atherothrombotic complications (Shah et al, 2018)
We identified a novel function of circPostn in promoting Myocardial infarction (MI)-induced myocardial injury and cardiac remodeling by modulating miR-96-5p/BNIP3 signaling
The Expression of circPostn Is Elevated in the Plasma of MI Patients and MI Models
Summary
Coronary heart disease is featured by the formation of stable atheromas that induce chronic myocardial ischemia or vulnerable plaques that lead to acute occlusive atherothrombotic complications (Shah et al, 2018). Circular RNAs (circRNAs) have been recognized as a novel type of regulatory RNAs with gene regulative functions, but their roles in cardiac injury and repair are not well-illustrated (Chen and Yang, 2015; Altesha et al, 2019). These closed covalent transcripts are produced when the pre-mRNA splicing machine back splices to enter the downstream 5 -splice sites to the upstream 3 -splice sites (Altesha et al, 2019). The role of circPostn in MI-induced myocardial injury and cardiac remodeling remains unclear
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