LncRNA Chaer Prevents Cardiomyocyte Apoptosis From Acute Myocardial Infarction Through AMPK Activation

Abstract

Long non-coding RNA (lncRNA) is widely reported to be involved in cardiac (patho)physiology. Acute myocardial infarction, in which cardiomyocyte apoptosis plays an important role, is a life-threatening disease. Here, we report the lncRNA Chaer that is anti-apoptotic in cardiomyocytes during Acute myocardial infarction. Importantly, lncRNA Chaer is significantly downregulated in both oxygen-glucose deprivation (oxygen-glucose deprivation)-treated cardiomyocytes in vitro and AMI heart. In vitro, overexpression of lncRNA Chaer with adeno virus reduces cardiomyocyte apoptosis induced by OGD-treated while silencing of lncRNA Chaer increases cardiomyocyte apoptosis instead. In vivo, forced expression of lncRNA Chaer with AAV9 attenuates cardiac apoptosis, reduces infarction area and improves mice heart function in AMI. Interestingly, overexpression of lncRNA Chaer promotes the phosphorylation of AMPK, and AMPK inhibitor Compound C reverses the overexpression of lncRNA Chaer effect of reducing cardiomyocyte apoptosis under OGD-treatment. In summary, we identify the novel ability of lncRNA Chaer in regulating cardiomyocyte apoptosis by promoting phosphorylation of AMPK in AMI.

Advances in Intercellular Communication Mediated by Exosomal ncRNAs in Cardiovascular Disease

“…lncRNA Chaer was significantly down-regulated in hypoxia-treated cardiomyocytes and in the hearts of myocardial infarction [35]. In vitro overexpression of lncRNA Chaer reduced hypoxia-induced cardiomyocyte apoptosis; conversely, silencing of lncRNA Chaer promoted cardiomyocyte apoptosis [35]. In vivo overexpression of lncRNA Chaer slowed myocyte apoptosis, reduced the infarcted area, and improved cardiac function in infarcted mice, suggesting that lncRNA Chaer has a protective effect against myocardial infarction [35].…”

“…In vitro overexpression of lncRNA Chaer reduced hypoxia-induced cardiomyocyte apoptosis; conversely, silencing of lncRNA Chaer promoted cardiomyocyte apoptosis [35]. In vivo overexpression of lncRNA Chaer slowed myocyte apoptosis, reduced the infarcted area, and improved cardiac function in infarcted mice, suggesting that lncRNA Chaer has a protective effect against myocardial infarction [35]. lncRNA Nron expression was elevated in the peripheral blood of myocardial infarcted patients and in hypoxia-stimulated H9c2 cells [36].…”

“…It was shown that lncRNA H19 promoted the development of atherosclerosis by promoting the MAPK and NF-kB signaling pathways [34]. lncRNA Chaer was significantly down-regulated in hypoxia-treated cardiomyocytes and in the hearts of myocardial infarction [35]. In vitro overexpression of lncRNA Chaer reduced hypoxia-induced cardiomyocyte apoptosis; conversely, silencing of lncRNA Chaer promoted cardiomyocyte apoptosis [35].…”

Behind the scenes: How RNA orchestrates the epigenetic regulation of gene expression

“…Chaer -PRC2 interaction is transiently promoted by the mammalian target of rapamycin (mTOR) pathway upon stress or hormonal stimuli and ultimately results in the induction of the genes responsible for heart hypertrophy ( Wang et al, 2016 ). Moreover, a recent work showed that Chaer is significantly downregulated in cardiomyocytes of a murine acute myocardial infarction model and that its overexpression, both in vitro and in vivo , reduces cardiomyocyte apoptosis and heart function impairment through a mechanism dependent on AMP-activated protein kinase (AMPK) phosphorylation ( He et al, 2021 ). Several other lncRNAs have been associated with cardiac mesoderm development, including Braveheart ( Bvht ) and cardiac mesoderm enhancer-associated non-coding RNA ( CARMEN ).…”

Programmed Cell Death: Complex Regulatory Networks in Cardiovascular Disease

“…For instance, Wu et al found that bradykinin (BK) could reduce myocardial apoptosis by reducing caspase-3 expression in a human cardiac c-Kit + progenitor cell (hCPCs) myocardial infarction model, thereby improving ischemic heart disease (Wu et al, 2021a), Uberti F et al showed that levosimendan could interfere with mitochondrial function by regulating mitoK (ATP) channels and NO, and could control the interaction between autophagy and apoptosis to protect H9c2 cells against oxidative damage (Uberti et al, 2011), Nie et al reported that lncRNA AK006774 could reduce I/R-induced infarct size and myocardial apoptosis by regulating Bcl-2 expression through miR-448 in a mouse I/R model (Nie et al, 2021), Xu et al found that GSK-3β upregulated CD47 expression in cardiac tissues after MI by activating NF-κb, and then regulated apoptosis leading to myocardial injury (Xu et al, 2021). Besides, AKT1/GSK3β, NF-κb, and other related signaling molecules can also regulate apoptosis in cardiovascular diseases (Supplementary Table S1) (Shen et al, 2020;Jiang et al, 2021a;Wang et al, 2021a;Jiang et al, 2021b;He et al, 2021;Lu et al, 2021;Sun et al, 2021;Xiong et al, 2021;Xu et al, 2021).…”