Differential expression of miR‐142‐3p protects cardiomyocytes from myocardial ischemia‐reperfusion via TLR4/NFkB axis

Abstract

Abstract Our research aims to explore the impact of miR‐142 on myocardial apoptosis in the mouse ischemia and reperfusion (IR) model and investigate the underlying mechanisms at the molecular level. A considerable downregulation of miR‐142 was observed in the cardiac area of mice post IR modeling. To understand the regulatory function of IR‐induced miR‐142 downregulation, the animals were categorized into four groups: IR model group; IR + agomir‐142 group (IR mice treated with agomir‐142); IR + antagomir‐142 group (IR mice treated with antagomir‐142); IR + agomir‐142 + negative control (NC) group (IR mice processed with agomir‐NC). The results indicated that agomir‐142 upregulation was capable of shrinking IR damage‐triggered infarction of the ventriculus sinister, strengthening myocardial function, and guarding against cardiomyocyte apoptosis, whereas further decreased miR‐142 with antagomir‐142 infection displayed negative influence of miR‐142 against mice IR damage. In the cellular assay, miR‐142 overexpression significantly improved proliferation and inhibited the apoptosis of neonatal rat cardiomyocytes (NRCs). Moreover, we found that miR‐142 reduced the Bcl‐2/Bax ratio and upregulated hydrogen peroxide (H 2 O 2 )‐induced caspase‐3 expression. Furthermore, transfection with an miR‐142 mimic prevented the upregulation of TLR4/NFkB expression and activation in H 2 O 2 ‐treated NRCs. Our findings also revealed that miR‐142 is linked to the 3'‐untranslated area of the TLR4 gene. In addition, TLR4 overexpression considerably ablated the protective effects of miR‐142 in terms of the cell viability of H 2 O 2 ‐treated NRCs. Taken together, miR‐142 agomir injection in mice and miR‐142 mimic transfection in NRCs plays a role in protecting the heart from IR damage and malfunction via the TLR4/NFkB axis both in vivo and in vitro.