IMR Press / RCM / Volume 22 / Issue 3 / DOI: 10.31083/j.rcm2203113
Open Access Original Research
Histone deacetylase inhibitor, mocetinostat, regulates cardiac remodelling and renin-angiotensin system activity in rats with transverse aortic constriction-induced pressure overload cardiac hypertrophy
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1 Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 41944 Daegu, Republic of Korea
2 Emerging Infectious Disease Vaccines Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 28159 Cheongju, Republic of Korea
3 Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Pusan National University School of Medicine, 49241 Busan, Republic of Korea

Academic Editor: Brian Tomlinson
This article belongs to the Special Issue: State-of-the-Art Cardiovascular Medicine in Asia 2021 (https://rcm.imrpress.com/EN/subject/listSubjectChapters.do?subjectId=1621394403410).

Rev. Cardiovasc. Med. 2021 , 22(3), 1037–1045; https://doi.org/10.31083/j.rcm2203113
Submitted: 5 July 2021 | Revised: 17 August 2021 | Accepted: 20 August 2021 | Published: 24 September 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Histone deacetylase (HDAC) inhibitors have shown cardioprotective or renoprotective effects in various animal models. Our study proposed that the HDAC inhibitor, mocetinostat, regulates cardiac remodelling and renin-angiotensin system (RAS) activity in rats with transverse aortic constriction (TAC)-induced pressure overload cardiac hypertrophy. Cardiac remodelling was evaluated using echocardiography. Cardiac hypertrophy was visualized with haematoxylin and eosin staining, and related gene (Nppa and Nppb) expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Cardiac and renal fibrosis were visualized with picrosirius red and trichrome staining, respectively. Fibrosis related gene (Collagen-1, Collagen-3, Ctgf, and Fibronectin) expression was determined by qRT-PCR. Serum concentrations of RAS components (renin, angiotensin II, and aldosterone) were quantified by enzyme-linked immunosorbent assay and related gene (Renin and Agtr1) expression was determined by qRT-PCR. TAC-induced pressure overload cardiac hypertrophy, which mimics hypertensive heart disease, increased cardiac remodelling, cardiac hypertrophy, and fibrosis in our rat models. Upon treatment with mocetinostat, there was a significant regression in cardiac remodelling, cardiac hypertrophy, and fibrosis in TAC rats. Additionally, pressure overload-induced renal fibrosis and activity of RAS-related components were increased in TAC rats, and were decreased on treatment with mocetinostat. The present study indicates that mocetinostat, an HDAC inhibitor, has cardiorenal protective effects in rats with TAC-induced pressure overload cardiac hypertrophy and offers a promising therapeutic agent for hypertension-related diseases.

Keywords
Animal model
Fibrosis
Heart
Histone deacetylase
Hypertension
Hypertrophy
Kidney
Figures
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