P5381Rev-erb receptor agonist improves cardiac function through modulating inflammatory processes in myocardial infarction

Introduction: Myocardial infarction (MI) initiates an inflammatory response that is essential for cardiac repair, but which is implicated in the pathogenesis of adverse cardiac remodelling, heart failure, and cardiac rupture. Rev-erb receptor, called as NR1D, modulates glucose and lipid metabolism and inflammatory response. Recently, a synthetic rev-erb receptor agonist SR9009 has been reported to improve hyperglycemia, dyslipidemia, and skeletal muscle oxidative function. However, the pathophysiological role of rev-erb receptor in MI remains to be investigated. Purpose: We aimed to investigate the roles of rev-erb receptor in cardiac remodelling after MI. Methods: Male wild-type C57BL6 mice underwent permanent surgical ligation of the left coronary artery to make MI model or sham-operation as a control. We firstly confirmed the time course of gene expression of rev-erb receptor in the left ventricles (LVs) after MI. Next, we divided mice into the following four groups: MI treated with vehicle (MI+V), MI treated with SR9009 (MI+SR), Sham-treated with vehicle (Sh+V), and Sham-treated with SR9009 (Sh+SR). Mice were intraperitoneally injected with vehicle or rev-erb receptor agonist SR9009 from 1 day before surgery throughout the experiment. Cardiac function was assessed by echocardiography on 7 days after surgery. The expression levels of inflammatory-related genes in the LVs were determined by using real-time PCR. Flow cytometric analysis was performed 1 and 5 days after MI to investigate the infiltration of the immune cells into the infarcted LVs. Finally, LV tissues were stained with Masson's trichrome, and immunohistochemistry.