MicroRNA‑1 downregulation induced by carvedilol protects cardiomyocytes against apoptosis by targeting heat shock protein 60

Abstract

Myocardial infarction (MI) is the most common event in cardiovascular disease. Carvedilol, a β-blocker with multiple pleiotropic actions, is widely used for the treatment cardiovascular diseases. However, the underlying mechanisms of carvedilol on alleviating MI are not fully understood. The aim of the present study was to investigate whether the beneficial effects of carvedilol were associated with regulation of microRNA-1 (miR-1). It was demonstrated that carvedilol ameliorated impaired cardiac function and decreased infarct size in a rat model of MI induced by coronary artery occlusion. Similarly, carvedilol reversed the H 2 O 2 -induced decrease in cardiomyocyte viability in a dose-dependent manner. The in vivo and in vitro models demonstrated the downregulation of miR-1 following treatment with carvedilol. Overexpression of miR-1, a known pro-apoptotic miRNA, decreased cell viability and induced cell apoptosis. Transfection of miR-1 abolished the beneficial effects of carvedilol. The expression of heat shock protein 60 (HSP60), a direct target of miR-1, was identified to be decreased in MI and H 2 O 2 -induced apoptosis, which was associated with a decrease in Bcl-2 and an increase in Bax; expression was restored following treatment with carvedilol. It was concluded that carvedilol partially exhibited its beneficial effects by downregulating miR-1 and increasing HSP60 expression. miR-1 has become a member of the group of carvedilol-responsive miRNAs. Future studies are required to fully elucidate the potential overlapping or compensatory effects of known carvedilol-responsive miRNAs and their underlying mechanisms of action in the pathophysiology of cardiovascular diseases.

Co-enzyme Q10 protects primary chicken myocardial cells from heat stress by upregulating autophagy and suppressing the PI3K/AKT/mTOR pathway

“…We found that treatment with co-enzyme Q10 alone did not influence the viability of myocardial cells, demonstrating that co-enzyme Q10 may be a safe drug to use to protect chickens from heat stress (Xu et al 2017a). Consistent with previous studies, we found that heat stress reduced the viability of primary chicken myocardial cells (Wang et al 2017;Hu et al 2019;Liu et al 2019); this reduced viability may be associated with the generation and accumulation of ROS that can result in increased oxidative damage (He et al 2019;Tiwari et al 2019). Pretreatment with co-enzyme Q10 significantly suppressed the decline in cell viability during heat stress, reduced cell apoptosis, and reduced ROS generation induced by heat stress.…”

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

“…MiR-1 is deemed an important regulator in cardiac development and disease, more specifically, in the regulation of cardiomyocyte apoptosis in the latter. 186 They observed how miR-1…”

“…They observed how miR‐1 overexpression was associated with decreased cell viability and how the effect of carvedilol is to precisely counteract this result via downregulation of miR‐1 and thus exercising an antiapoptotic reaction 186 . In an effort to further analyze this mechanism, expression of HSP60 was measured, a target of miR‐1 186 . Carvedilol was able to increase mRNA expression levels of HSP60 while simultaneously downregulating miR‐1 expression 186 .…”

“…In an effort to further analyze this mechanism, expression of HSP60 was measured, a target of miR‐1 186 . Carvedilol was able to increase mRNA expression levels of HSP60 while simultaneously downregulating miR‐1 expression 186 . The resulting upregulation of HSP60 was linked to an upregulation of Bcl‐2 and downregulation of Bax 186 .…”

<p>Carvedilol Alters Circulating MiR-1 and MiR-214 in Heart Failure</p>

“…In addition, administration of a miR-1 mimic to rats with left ventricular hypertrophy causes reversion of cardiac hypertrophy and alleviation of fibrosis and apoptosis which are recognized to be a major feature of cardiac remodeling and HF. Although a report by Hu et al is suggestive of downregulation of miR-1 by means of carvedilol in an animal model of myocardial infarction (MI), 59 it seems that miRNAs play different roles in different species as well as different physiological and pathological conditions. 46,47 Altogether, it can be postulated that miR-1 may reduce cardiac hypertrophy, 60 that mediates the protective effects of carvedilol or at least this inference deserves further studies to obtain supporting evidence.…”