Pyroptosis inhibition improves the symptom of acute myocardial infarction

Abstract

AbstractAcute myocardial infarction (AMI), the leading cause of mortality worldwide, is a rapidly developing and irreversible disease. Therefore, proper prompt intervention at the early stage of AMI is crucial for its treatment. However, the molecular features in the early stage have not been clarified. Here, we constructed mouse AMI model and profiled transcriptomes and proteomes at the early stages of AMI progress. Immune system was extensively activated at 6-h AMI. Then, pyroptosis was activated at 24-h AMI. VX-765 treatment, a pyroptosis inhibitor, significantly reduced the infarct size and improved the function of cardiomyocytes. Besides, we identified that WIPI1, specifically expressed in heart, was significantly upregulated at 1 h after AMI. Moreover, WIPI1 expression is significantly higher in the peripheral blood of patients with AMI than healthy control. WIPI1 can serve as a potential early diagnostic biomarker for AMI. It likely decelerates AMI progress by activating autophagy pathways. These findings shed new light on gene expression dynamics in AMI progress, and present a potential early diagnostic marker and a candidate drug for clinical pre-treatment to prolong the optimal cure time.