Activation of AHR by ITE Improves Cardiac Remodelling and Function in Rats After Myocardial Infarction

作者：Xiaoyan Lin, Weiqiang Liu, Yong Chu, Hailin Zhang, Lishan Zeng, Yifei Lin, Kai Kang, Feng Peng, Jinxiu Lin, Chun‐Kai Huang, Dajun Chai · 发表于：ESC Heart Failure · 年份：2023 · DOI：10.1002/ehf2.14532 · 被引用次数：38 · 研究领域：Toxic Organic Pollutants Impact、Eicosanoids and Hypertension Pharmacology、Cardiac Ischemia and Reperfusion

Abstract Aims Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. Methods and results MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay; F4/80+iNOS+M1 macrophages and F4/80+CD206+M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P-Akt, p70S6K, P-p70S6K, Bcl-2, Bax, caspase-3, and cleaved caspase-3 protein levels were determined via Western blotting. We found tha...