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.

RIPK3 Induces Cardiomyocyte Necroptosis via Inhibition of AMPK‐Parkin‐Mitophagy in Cardiac Remodelling after Myocardial Infarction

“…MI mouse models were established according to a standard protocol: prior to surgery, wild-type (WT, male, 12 wk old, n = 60) and Ripk3 −/− mice were administered with inhalation anaesthesia by using 1–2% isoflurane. The ligation surgical procedure of left anterior descending coronary artery was done as reported [ 29 ]. As a control, the specific artery remained intact in the sham group in the operation.…”

Role of the ROS-JNK Signaling Pathway in Hypoxia-Induced Atrial Fibrotic Responses in HL-1 Cardiomyocytes

“…Increasing the activation of JNK could increase the mRNA expressions of collagen I, collagen III and MMP9 to cause cardiac fibrosis [ 43 ]. Decreasing ROS level under hypoxia condition could suppress JNK activation and the gene expression of CTGF, collagen I and III followed improvement of fibrosis [ 44 ]. However, these studies were not focusing on atrial cardiomyocytes.…”

The Serum of MEF2D Expression in Patients with Myocardial Infarction, May be Clinical Indicators and it Mediated ROS Signaling by HDAC5

“…MI leads to abnormal intracellular environment caused by insu cient energy supply [19]. The compensatory increase in cardiac contraction can cause the increase in ROS level caused by NADPH in the cell membrane [20]. More seriously, the increased ROS levels triggers the mitochondria to produce a large amount of ROS ("oxygen triggered-oxygen release" mechanism in mitochondria) [21].…”