Protective Role of (-)-Epicatechin on Trimethylamine-N-Oxide (TMAO)-Induced Cardiac Hypertrophy via SP1/SIRT1/SUMO1 Signaling Pathway.

Autor: Hong S; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Lu J; The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin, China.; Department of Pharmacy, First Affiliated Hospital, Harbin Medical University, Harbin, China., Li J; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.; Department of ECG Room, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, Shaanxi, China., Luo Y; Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin, China., Liu D; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Jin Y; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Wang Z; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Wang Y; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Zhang H; College of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei, China., Zhang X; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Li Y; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Zhang H; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China., Dong Z; The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin, China.; Department of Pharmacy, First Affiliated Hospital, Harbin Medical University, Harbin, China., Wang Z; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China. hyd2013@qq.com., Lv L; Experimental Animal Center, First Affiliated Hospital, Harbin Medical University, Harbin, China. dicklin1992@163.com., Liang Z; Department of Cardiology, First Affiliated Hospital, Harbin Medical University, No. 23 YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China. zhaoguangliangsupper@126.com.
Jazyk: angličtina
Zdroj: Cardiovascular toxicology [Cardiovasc Toxicol] 2024 Dec; Vol. 24 (12), pp. 1335-1347. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1007/s12012-024-09932-8
Abstrakt: (-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway.
Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical Approval The study was approved by the Institutional Ethics Committees of the First Affiliated Hospital of Harbin Medical University (No. IRB-AF/SC-08/05.0). The present study was conducted according to the “Guide for the Care and Use of Laboratory Animals” (NIH Publication No.85-23, revised in 1996). The animal experiments were approved by the Institutional Animal Care and Use Committee of First Affiliated Hospital, Harbin Medical University. Consent to Participate The study protocols and the procedures for handling human samples were approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (Harbin, China). All patients provided informed consent, and all the methods were carried out in accordance with the approved guidelines. Consent for Publication Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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