Abstract
Myocardial infarction (MI) damage induces various types of cell death, and persistent ischemia causes cardiac contractile decline. An effective therapeutic strategy is needed to reduce myocardial cell death and induce cardiac recovery. Therefore, studies on molecular and genetic biomarkers of MI, such as microRNAs (miRs), have recently been increasing and attracting attention due to the ideal characteristics of miRs. The aim of the present study was to discover novel causative factors of MI using multiomics-based functional experiments. Through proteomic, MALDI-TOF-MS, RNA sequencing, and network analyses of myocardial infarcted rat hearts and in vitro functional analyses of myocardial cells, we found that cytochrome c oxidase subunit 5a (Cox5a) expression is noticeably decreased in myocardial infarcted rat hearts and myocardial cells under hypoxic conditions, regulates other identified proteins and is closely related to hypoxia-induced cell death. Moreover, using in silico and in vitro analyses, we found that miR-26a-5p and miR-26b-5p (miR-26a/b-5p) may directly modulate Cox5a, which regulates hypoxia-related cell death. The results of this study elucidate the direct molecular mechanisms linking miR-26a/b-5p and Cox5a in cell death induced by oxygen tension, which may contribute to the identification of new therapeutic targets to modulate cardiac function under physiological and pathological conditions.
Highlights
Myocardial infarction (MI) is a type of coronary artery disease (CAD) caused by the death of myocardial cells and damage to cardiac muscle due to occlusion of coronary arteries[1,2]
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), RNA sequencing and network analyses of myocardial infarcted rat hearts and in vitro functional studies using myocardial cells, we found that cytochrome c oxidase subunit 5a (Cox5a) expression is noticeably decreased in myocardial infarcted rat hearts and myocardial cells under hypoxic conditions, regulates other identified proteins and is closely related to cell death induced by a decreased oxygen level
Forty-three spots showing significant differential expression between groups were identified among the 240 spots examined, and 22 different proteins were identified by peptide mass fingerprinting (PMF) (Table 1)
Summary
Myocardial infarction (MI) is a type of coronary artery disease (CAD) caused by the death of myocardial cells and damage to cardiac muscle due to occlusion of coronary arteries[1,2]. CAD is one of the major causes of morbidity and mortality and leads to more than seven million deaths worldwide annually[1]. Once the intravascular oxygen supply is blocked, MI is triggered within 20 min, and complete cell death occurs within a few hours[1,3]. Various studies have shown that MI damage induces various types of cell death, including necrosis, apoptosis, and autophagy[4,5]. We determined the presence of necroptotic and apoptotic cell death in association with cardiac ischemic injury and the inhibitory effects of microRNAs (miRs) on cell death[6].
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