Activation of Aryl Hydrocarbon Receptor by ITE Improves Cardiac Function in Mice After Myocardial Infarction

• Published in: Journal of the American Heart Association 2021-07, Vol.10 (13), p.e020502-e020502
• Main Authors: Seong, Eunhwa, Lee, Jun-Ho, Lim, Sungmin, Park, Eun-Hye, Kim, Eunmin, Kim, Chan Woo, Lee, Eunmi, Oh, Gyu-Chul, Choo, Eun Ho, Hwang, Byung-Hee, Kim, Chan Joon, Ihm, Sang Hyun, Youn, Ho Joong, Chung, Wook Sung, Chang, Kiyuk
• Format: Article
• Language: English
• Subjects: 2‐(1’H‐indole‐3’‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester; Animals; aryl hydrocarbon receptor; Basic Helix-Loop-Helix Transcription Factors - agonists; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Differentiation - drug effects; Cells, Cultured; Coculture Techniques; dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Disease Models, Animal; Indoles - pharmacology; Ligands; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - immunology; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocardium - immunology; Myocardium - metabolism; Myocardium - pathology; Original Research; Phenotype; Receptors, Aryl Hydrocarbon - agonists; Receptors, Aryl Hydrocarbon - metabolism; Recovery of Function; regulatory T cells; Signal Transduction; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Thiazoles - pharmacology; Ventricular Function, Left - drug effects; Wound Healing - drug effects
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.120.020502

Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2-[1'H-indole-3'-carbonyl]-thiazole-4-carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T-cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE-treated mice exhibited significantly improved systolic function (