Role of microRNA‐145 in protection against myocardial ischemia/reperfusion injury in mice by regulating expression of GZMK with the treatment of sevoflurane

Abstract

This study aims to investigate the role of microRNA‐145 (miR‐145) in protection against myocardial ischemia/reperfusion (I/R) injury in mice by regulating expression of granzyme K (GZMK) with the treatment of sevoflurane. The mice model of myocardial I/R injury was established by left coronary artery ligation. The expression of miR‐145 and GZMK in myocardial tissues of mice was detected by Reverse transcription quantitative polymerase chain reaction and western blot analysis. The changes of the cardiac function and hemodynamics, pathological changes of myocardial tissues, the ultrastructure of cardiomyocytes, myocardial infarction area, and cardiomyocyte apoptosis were observed. The expression of the apoptosis‐related protein cleaved‐caspase‐3, Bax, and Bcl‐2 was detected by western blot analysis. The levels of malondialdehyde, myeloperoxidase, superoxide dismutase in myocardial tissues were detected by spectrophotometric colorimetry. The levels of interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α in the serum of mice were detected by the enzyme‐linked immunosorbent assay. The level of oxidative stress and the expression of inflammatory factors increased in mice with myocardial I/R injury. Sevoflurane postconditioning could reduce myocardial I/R injury in mice. Sevoflurane postconditioning may protect myocardial I/R injury through miR‐145‐regulation of GZMK in mice. Inhibition of miR‐145 expression could reduce the protective effect of sevoflurane posttreatment on myocardial I/R injury in mice. Low expression of GZMK could attenuate the inhibitory effect of miR‐145 on myocardial I/R injury after sevoflurane treatment in mice. Our study suggests that sevoflurane postconditioning may protect against myocardial I/R injury by upregulating miR‐145 expression and downregulating GZMK expression.

MicroRNA‑145‑5p inhibits hypoxia/reoxygenation‑induced apoptosis in H9c2 cardiomyocytes by targeting ROCK1

“…For example, a previous study reported that miR-145-5p promoted the apoptosis of cardiomyocytes after myocardial I/R in rats (12). However, other studies demonstrated that miR-145-5p protected against myocardial I/R injury in murine models via anti-apoptotic, anti-inflammatory and autophagy pathways (10,11,29). Hence, the role of miR-145-5p in myocardial I/R injury remains unclear.…”

“…miR-145 is highly expressed in the vasculature and its role in the cardiovascular system has been extensively investigated (7)(8)(9). A few studies have explored the role of miR-145-5p in myocardial I/R (10)(11)(12). However, the results of these studies were inconsistent and the role of miR-145-5p in myocardial I/R remains elusive.…”

Intracellular and Extracellular Roles of Granzyme K

“…As GrK is a potential target gene of miRNA-145, miRNA-145 could inhibit GrK expression. Upon treatment with sevoflurane, miRNA-145 levels are upregulated and GrK expression is reduced – relieving I/R injury ( 90 ). Interestingly, miRNA-145 significantly elevates functioning of the left ventricle and decreases the myocardial infarct size suggesting that downregulation of GrK and upregulation of miRNA-145 may be protective of I/R injury ( 90 ).…”

MicroRNA-145 Protects against Myocardial Ischemia Reperfusion Injury via CaMKII-Mediated Antiapoptotic and Anti-Inflammatory Pathways

“…Furthermore, Yuan et al [10] proved that miR-145 exerted a cardioprotective effect in myocardial I/R injury by ameliorating inflammation via regulation of CD40 in vitro. Moreover, prior studies [9, 11] have demonstrated that antagonizing miR-145 pretreatment significantly aggravated myocardial I/R injury by deteriorating infarcted myocardium size, apoptosis, and inflammation in mouse. Although miR-145 may represent a novel potential therapeutic target, its role in cardiac I/R injury in vivo is still unclear.…”