Crim1 suppresses left ventricular hypertrophy

• Type of Material: Article
• Authors: Long Yang, Guizhou Provincial People's Hospital; Jionghong He, Guizhou Provincial People's Hospital; Guiling Xia, Guizhou Provincial People's Hospital; Jun Yang, Guizhou Provincial People's Hospital; Qian Tang, Guizhou Provincial People's Hospital; Yongyao Yang, Guizhou Provincial People's Hospital; Jiusheng Deng, Emory University
• Language: English
• Date: 2019-06-01
• Publisher: Spandidos Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2019, Spandidos Publications. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.3892/br.2019.1214
• Title of Journal or Parent Work: Biomedical Reports
• ISSN: 2049-9434
• Volume: 10
• Issue: 6
• Start Page: 343
• End Page: 350
• Grant/Funding Information: This study was supported by grants from the Guizhou Provincial Science and Technology Fund [grant no. (2019) 1209], the Chinese National Natural Science Foundation to YL (grant no. 81260040), the Chinese National Clinical Key Specialty Construction Project to YL [grant no. (2013) 544] and the Clinical Research Center Project of Department of Science & Technology of Guizhou Province, China to YL [grant no. (2017) 5405].
• Keywords: abdominal aortic coarctation; left ventricular hypertrophy; cysteine-rich transmembrane bone morphogenetic protein regulator 1; telmisartan
• Research Categories: Biology, Genetics; Health Sciences, Pathology

Abstract

Left ventricular hypertrophy is a leading cause of heart failure and sudden death. Cysteine-rich transmembrane bone morphogenetic protein regulator 1 (Crim1) is expressed at a high level in the heart and has a regulatory role in heart development. The present study aimed to test the hypothesis that Crim1 can have an inhibitory function on ventricular hypertrophy. Rat primary ventricular myocytes were stretched to induce myocyte hypertrophy, and treated with telmisartan or infected with Crim1-expressing recombinant adenovirus (Ad-Crim1). Rat ventricular hypertrophy was induced by abdominal aortic coarctation (AAC), and treated either with telmisartan or myocardial injection of Ad-Crim1 or empty adenovirus vector. The results showed that the expression of Crim1 decreased in the hypertrophic ventricle. The inhibition of angiotensin receptor type 1 (AT1R) by telmisartan in vitro and in vivo significantly increased the expression of Crim1 in the left ventricle. The overexpression of Crim1 by infection with Ad-Crim1 significantly inhibited stretch-induced ventricular myocyte hypertrophy in vitro. The overexpression of Crim1 by gavage with AT1R inhibitor telmisartan or myocardial injection of Ad-Crim1 markedly suppressed AAC-induced left ventricular hypertrophy in vivo. These results suggest that Crim1 has a suppressive function on ventricular hypertrophy and provides a novel therapeutic target for the treatment of cardiac hypertrophy.