Bromodomain-containing protein 7 contributes to myocardial infarction-induced myocardial injury through activating Wnt/β-catenin signaling.

Abstract

Myocardial infarction (MI) is one of the most common cardiovascular diseases, inducing severe myocardial injury and leading to high mortality. Bromodomain-containing protein 7 (BRD7), a member of bromodomain-containing protein family, is involved in multiple cellular processes, such as cell cycle, transcriptional regulation, and chromatin remodeling, but the functions of BRD7 in regulating MI-associated myocardial injury are still obscure. In this work, we investigated the effect of BRD7 on MI-induced myocardial injury in vitro and in vivo. The MI model was established by ligating the left anterior descending coronary artery (LAD) of rats which were then injected with BRD7 short hairpin RNA (shRNA). The rat H9C2 cardiomyocytes were treated with hypoxia and injected with BRD7 shRNA. The expression of BRD7 in MI rat model, and hypoxia-treated H9C2 cells was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemical staining. The effect of BRD7 was analyzed using western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, echocardiography, and flow cytometry analysis. The expressions of Wnt/β-catenin signaling relative proteins were determined by western blot. Significantly, BRD7 was highly expressed in MI patients, MI rat models, and hypoxia treated rat H9C2 cardiomyocytes. Echocardiography analysis demonstrated that the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were repressed in the MI rats relative to sham group rats, while the silencing of BRD7 rescued the dysfunction in the model. We also found that BRD7 silencing reduced cardiomyocyte apoptosis in both MI rats and H9C2 cells under the treatment of hypoxia. BRD7 silencing inhibited the activation of Wnt/β-catenin signaling in H9C2 cells under the treatment of hypoxia. Moreover, Wnt agonist BML294 reversed the anti-apoptosis effect of BRD7 silencing in hypoxia-induced H9C2 cells. Collectively, we concluded that BRD7 contributed to MI-induced myocardial injury through activating Wnt/β-catenin signaling. Targeting BRD7 may become a promising therapeutic strategy for the treatment of MI-induced myocardial injury.