Cardiometabolic Modulation by Semaglutide Contributes to Cardioprotection in Rats with Myocardial Infarction

作者：Haihao Yan, Wenjing Yao, Yanhong Li, Tianxing Li, Kexin Song, Pan Yan, Yi Dang · 发表于：Drug Design Development and Therapy · 年份：2024 · DOI：10.2147/dddt.s491970 · 被引用次数：4 · 研究领域：Cardiovascular Function and Risk Factors、Cardiac Ischemia and Reperfusion、Hyperglycemia and glycemic control in critically ill and hospitalized patients

Background: Acute myocardial infarction (AMI) is a significant clinical challenge. Semaglutide has therapeutic potential in cardiovascular disease management, but its specific impact and mechanisms in AMI are not fully understood. Methods: Twenty-four male Sprague-Dawley rats were divided into three groups: control (Control), infarction-only (MI), and semaglutide-treated (SEMA). Weight, blood glucose, and lipid profiles were analyzed. Cardiac function was evaluated via echocardiography. Histopathological assessment and immunohistochemical analysis were performed. Untargeted metabolomic analysis using LC-MS/MS was utilized. Results: Semaglutide treatment was associated with a reduction in body weight, blood glucose, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), as well as an enhancement in the left ventricular ejection fraction (Control vs MI vs SEMA, 69.13±4.30 vs 30.16±3.17 vs 39.81±6.13, P < 0.05). It also had a lower collagen volume fraction (3.05 vs 34.05 vs 17.73, P < 0.05) and ameliorated the accumulation of glycogen in the myocardium. Metabolomic profiling revealed differentially expressed metabolites between the control/MI and MI/SEMA groups, predominantly within benzenoid, lipid, and organic acid categories. Pathway enrichment analysis highlighted amino sugar and nucleotide sugar metabolism, chlorocyclohexane and chlorobenzene degradation, and phenylalanine, tyrosine, and tryptophan biosynthesis. Random forest analysis identified key metabo...