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Histone deacetylase inhibitor CG200745 ameliorates high-fat diet-induced hypertension via inhibition of angiotensin II production

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Affiliated Author(s)
이윤한장병철김지인
Alternative Author(s)
Lee, Yun HanJang, Byeong ChurlKim, Jee In
Journal Title
Naunyn-Schmiedeberg's archives of pharmacology
ISSN
1432-1912
Issued Date
2020
Keyword
HDAC inhibitorObesityHypertensionAng IIHDAC activity
Abstract
Obesity is growing rapidly worldwide due to consumption of westernized diet and lack of exercise. Obesity is one of the major risk factors of hypertension. The novel histone deacetylase (HDAC) inhibitor CG200745 was originally developed to treat various cancers. Previous studies showed that CG200745 attenuated hypertension through inhibition of cardiac hypertrophy and fibrosis in deoxycorticosterone acetate-induced hypertensive rat. The purpose of this study is to investigate the role and underlying mechanism of CG200745 in high-fat diet (HFD)-induced hypertension. Nine-week old C57BL/6 mice were fed a normal diet (ND) or HFD for 17 weeks. Each group of mice was treated with vehicle or CG200745 by intraperitoneal injection for 9 days. HFD group showed higher body weight, blood pressure (BP), HDAC activities, angiotensinogen and renin expressions in kidney, angiotensin-converting enzyme (ACE) expression in the lung, serum angiotensin II (Ang II) concentration, and myosin light chain20 (MLC20) phosphorylation in mesenteric artery compared with ND group. CG200745 lowered BP, HDAC activity, renin and angiotensinogen in the kidney, ACE in the lung, serum Ang II level, and phosphorylation of MLC20 in HFD group. In conclusion, CG200745 ameliorated HFD-induced hypertension through inhibition of HDAC/Ang II/vascular contraction axis. Our results offer CG200745 as a novel therapeutic option for HFD-induced hypertension.
Department
Dept. of Molecular Medicine (분자의학)
Publisher
School of Medicine (의과대학)
Citation
Ga-Eun Yoon et al. (2020). Histone deacetylase inhibitor CG200745 ameliorates high-fat diet-induced hypertension via inhibition of angiotensin II production. Naunyn-Schmiedeberg’s archives of pharmacology, 393(3), 491–500. doi: 10.1007/s00210-019-01749-5
Type
Article
ISSN
1432-1912
DOI
10.1007/s00210-019-01749-5
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43251
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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