miR-129-5p ameliorates ischemia-reperfusion injury by targeting HMGB1 in myocardium

Abstract

Globally, acute myocardial infarction (AMI) is a serious condition affecting millions of individuals. While AMI therapy improves blood flow during surgery, reperfusion-induced injury may also occur, leading to secondary cardiac damage or even death. Here, we investigated miR-129-5p in myocardial ischemia-reperfusion (I/R) injury in rats, to explore reperfusion-related molecular mechanisms in myocardium. We used Sprague Dawley rats to establish a myocardial I/R model, with agomiR-129-5p injection, and used rat cardiomyocytes (H9c2) treated with anoxia-reoxygenation (A/R) to mimic myocardial I/R injury in vitro. A dual-luciferase reporter assay determined miR-129-5p binding to high mobility group box-1 (HMGB1) in H9c2 cells. We showed that exogenous miR-129-5p restored cardiac function indices, alleviated cardiac injury, relieved inflammatory effects and reduced infarct size and cell apoptosis in rat myocardium after I/R treatment. Elevated miR-129-5p induced a reduction in HMGB1 expression in rat I/R myocardium. miR-129-5p also targeted HMGB1, and negatively regulated its expression in H9c2 cells. Moreover, miR-129-5p overexpression in the cardiomyocytes reduced cell apoptosis and recovered cell viability after A/R injury, which was reversed by subsequent HMGB1 overexpression. These findings suggest miR-129-5p plays a cardioprotective role in ameliorating myocardial I/R injury in rats, by negatively targeting HMGB1. This mechanism provides new insights into the treatment of myocardium reperfusion-related damage.

Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs—A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial

“…However, prior to finding such an innovative method for subsequent treatment of AMI just after the primary PCI procedure, the pathophysiological mechanism of myocardial damage/death prior to and after primary PCI should be more thoroughly clarified ( 4 ). According to the reports from basic and clinical research ( 1 , 4 , 17 – 24 ), it is reasonable to believe that at least six cardinal reasons for myocardial damage: (1) myocardial necrosis due to complete loss of the blood supply prior to primary PCI, (2) ischemia-reperfusion injury, (3) AMI-elicited rigorous inflammatory reaction, (4) immune hyper-reactivity (i.e., overwhelming immune response), (5) inflammatory cell infiltration and proinflammatory cytokine release in infarct/peri-infarct areas, and (6) generations of reactive oxygen species (ROS)/free radicals which cause oxidative stress after AMI.…”

Endocardial HDAC3 is required for myocardial trabeculation

“…miR-129-5p plays important roles in cancer by either promoting or inhibiting tumorigenesis through regulating a variety of downstream targets and pathways 61, 62 . Several studies have shown that miR-129-5p protects adult hearts from ischemia/reperfusion injuries 63, 64 , while another study demonstrated that treating cultured H9c2 cardiomyocytes with HDAC pan-inhibitor Trichostatin A results in decreased cardiomyocyte proliferation with enhanced miR-129-5p expression 65 . This is consistent with our current findings in the developing endocardium (Figure 4).…”

Lncrna FGD5-AS1 Aggravates Myocardial Ischemia-Reperfusion Injury by Sponging Mir-129-5p

“…Consistent with our study, miR-129-5p alleviates myocardial injury after ischemia/reperfusion ( 17 ). miR-129-5p ameliorated ischemia-reperfusion injury by targeting HMGB1 in myocardium ( 18 ). All these results indicate that miR-129-5p play a positive effect on myocardial I/R injury.…”