演讲嘉宾

Dr. Weihong He, Associate Professor

Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

Biography: Dr. Weihong He is a principal investigator and Associate Professor at the Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University. Dr. Weihong He obtained an MD (2012) at West China School of Medicine & West China Hospital, Sichuan University, and completed a PhD (2017) at the BHF Glasgow Cardiovascular Research Centre, University of Glasgow. He was an associate professor at Jining Medical University (2018-2020). Since 2020, he has led a research group to study the pathophysiology of cardiovascular diseases and to investigate novel therapeutic drugs for myocardial infarction and cerebral infarction at Sichuan University. He also teaches physiology and mentors both national and international students. He has expertise in many methodologies which span the level of biochemistry, cell biology, isolated heart, and whole animal in vivo disease models.

Topic: Inhibiting RUNX1 Leads to Reduced Infarct Size and Repressed Cardiac Cathepsin Levels Following Acute Myocardial Infarction

Abstract: Acute myocardial infarction (MI) is a leading cause of death worldwide. Acute MI results in prolonged myocardial ischemia and the subsequent cell death leads to heart failure which is linked with increased deaths or hospitalizations. Cathepsins are lysosomal proteases involved in protein degradation and can also be secreted into extracellular spaces. Recent evidence has shown that cardiac release of a subtype of cathepsin (cathepsin-L) in MI patients leads to elevated serum cathepsin-L levels which are associated with reduced cardiac function and increased infarct size. However, the mechanism of the increased cathepsin-L level is unknown. Runt-related transcription factor-1 (RUNX1) is a master-regulator transcription factor, which is implicated in the transcriptional regulation of gene expression. Recent evidence demonstrated that RUNX1 plays a critical role in the heart after MI. This work sought to investigate whether inhibition of RUNX1 affects cathepsin levels in a rat MI model. MI was surgically induced by performing coronary artery ligation. Heart samples were taken at 24 hours post-MI and analyzed by LC-MS/MS operating in the data-independent acquisition (DIA) mode. We found that overall cathepsin levels were increased in control hearts after MI. In contrast, rats treated with RUNX1 inhibitors demonstrated decreased cathepsin levels. Furthermore, RUNX1 inhibition led to a reduced infarct size at 24 hours post-MI as determined through 2,3,5-triphenyltetrazolium chloride (TTC) staining. These results are in line with Dr. He’s previous study performed in isolated rat hearts which demonstrates that inhibition of cathepsin-L reduces infarct size and improves cardiac function ex vivo. The present study shows that inhibition of RUNX1 after acute MI can also reduce infarct size in rat hearts in vivo and the beneficial effects may be achieved by repressed cathepsin levels, thus suggesting the translational potential of RUNX1 and cathepsins as therapeutic targets of cardiac protection against acute MI.