Zinc Finger Protein ZBTB20 protects against cardiac remodelling post-myocardial infarction via ROS-TNFα/ASK1/JNK pathway regulation

Abstract

This study aims to determine the efficacy of Zinc finger protein ZBTB20 in treatment of post-infarction cardiac remodelling. For this purpose, left anterior descending (LAD) ligation was operated on mice to induce myocardial infarction (MI) with sham control group as contrast and adeno-associated virus (AAV9) system was used to deliver ZBTB20 to mouse heart by myocardial injection with vehicle-injected control group as contrast two weeks before MI surgery. Then four weeks after MI, vehicle-treated mice with left ventricular (LV) remodelling underwent deterioration of cardiac function, with symptoms of hypertrophy, interstitial fibrosis, inflammation and apoptosis. The vehicle-injected mice also showed increase of infarct size and decrease of survival rate. Meanwhile, the ZBTB20-overexpressed mice displayed improvement after MI. Moreover, the anti-apoptosis effect of ZBTB20 was further confirmed in H9c2 cells subjected to hypoxia in vitro. Further study suggested that ZBTB20 exerts cardioprotection by inhibiting tumour necrosis factor α/apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase 1/2 (JNK1/2) signalling, which was confirmed by shRNA-JNK adenoviruses transfection or a JNK activator in vitro as well as ASK1 overexpression in vivo. In summary, our data suggest that ZBTB20 could alleviate cardiac remodelling post-MI. Thus, administration of ZBTB20 can be considered as a promising treatment strategy for heart failure post-MI. Significance Statement: ZBTB20 could alleviate cardiac remodelling post-MI via inhibition of ASK1/JNK1/2 signalling.

Keywords: ASK1/JNK1/2; ZBTB20; apoptosis; cardiac remodelling; myocardial infarction.