Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Abstract

BackgroundMyocardial infarction (MI) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor‐β receptor III (TGFβR3) on cardiomyocyte apoptosis during MI.Methods and ResultsAn MI mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis, TGFβR3, and mitogen‐activated protein kinase signaling were assessed by methylthiazolyldiphenyl‐tetrazolium bromide assay, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that TGFβR3 expression in the border region of the heart was dynamically changed during MI. After stimulation with H2O2, TGFβR3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas TGFβR3 knockdown had the opposite effect. ERK1/2 and JNK1/2 signaling was not altered by TGFβR3 modulation, and p38 inhibitor (SB203580) reduced the effect of TGFβR3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in vitro observations, cardiac TGFβR3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon MI. Conversely, cardiac loss of function of TGFβR3 by adeno‐associated viral vector serotype 9–TGFβR3 short hairpin RNA attenuated the effects of MI in mice.Conclusions TGFβR3 promotes apoptosis of cardiomyocytes via a p38 pathway–associated mechanism, and loss of TGFβR3 reduces MI injury, which suggests that TGFβR3 may serve as a novel therapeutic target for MI.

Endophilin A2-mediated alleviation of endoplasmic reticulum stress-induced cardiac injury involves the suppression of ERO1α/IP3R signaling pathway

“…Due to a loss of terminally differentiated cardiomyocytes, which is dedicated to wall thinning, ventricular dilatation and fibrosis, apoptosis is a critical contributor to heart failure. It has been reported that TGFβR3 protected ischemia-induced cardiomyocyte apoptosis via activation p38 signaling pathway, whereas loss of TGFβR3 reduced apoptosis and improved cardiac function [37]. Our recently published study verified that EndoA2 attenuated H2O2-induced rat basilar artery smooth muscle cell apoptosis [18].…”

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

“…Then, the supernatant was discarded and 150 μL of DMSO was added to dissolve the formazan crystals. The microplate reader (BioTek, USA) was used to measure absorbance value at 490 nm …”

Knockdown of endogenous RNF4 exacerbates ischaemia‐induced cardiomyocyte apoptosis in mice

“…To investigate the role of RNF4 in heart disease, GFP‐labelled AAV9‐shRNA targeting RNF4 was delivered into the heart to specifically knockdown cardiac endogenous RNF4 via in vivo adeno‐associated virus infection, which is a well‐established experimental technique used in cardiovascular research 20‐22 . After two weeks, successful infection was demonstrated by green‐stained myocardia in the Scramble‐ and shRNF4‐treated groups (Figure ), and endogenous RNF4 was reduced by 41% compared with that of the Scramble group (Figure 5A).…”