表儿茶素通过 SP1/SIRT1/SUMO1 信号通路对三甲胺氧化物 (TMAO) 诱导的心肌肥大的保护作用

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Toxicology Pub Date : 2024-10-17 DOI:10.1007/s12012-024-09932-8
Siting Hong, Jing Lu, Jiaoyan Li, Yingchun Luo, Dongxue Liu, Yuanyuan Jin, Zeng Wang, Yibo Wang, Hao Zhang, Xin Zhang, Yang Li, Haoruo Zhang, Zengxiang Dong, Zhaojun Wang, Lin Lv, Zhaoguang Liang
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引用次数: 0

摘要

(-)-表儿茶素(EPI)有益于心血管健康。三甲胺 N-氧化物(TMAO)是一种源自肠道微生物的食物代谢物,与心血管疾病风险密切相关。然而,EPI对TMAO诱导的心脏肥大的影响和潜在机制仍不清楚。本研究旨在确定 EPI 是否能抑制 TMAO 诱导的心脏肥大。研究人员测量并分析了对照组和心肌肥厚患者血浆中的 TMAO 水平。雄性 C57BL/6 小鼠被随机分为对照组、TMAO 组、EPI 组和 TMAO + EPI 组。按照分组,小鼠腹腔注射生理盐水或腹腔注射TMAO(150毫克/千克/天),连续14天。EPI 组单独胃内注射 EPI(1 毫克/千克/天)21 天,TMAO + EPI 组胃内注射 EPI 7 天后开始胃内注射 TMAO,直至 TMAO 治疗结束。通过H&E和Masson染色对小鼠心脏进行组织学分析。在体外,用TMAO(10 µM)诱导H9c2细胞肥大24小时,并用或不用EPI(10 µM)预处理1小时。心脏肥大患者血浆中的TMAO水平为2.66 ± 1.59 μmol/L,对照组为0.62 ± 0.30 μmol/L。EPI 可减轻 TMAO 诱导的 H9c2 细胞肥大。在体内,TMAO诱导小鼠心脏肥大并损害其心脏功能。病理染色显示,TMAO诱导小鼠心脏肥大和胶原沉积。EPI 治疗可改善心功能,抑制 TMAO 诱导的心肌肥厚。在体内和体外,EPI能明显降低TMAO诱导的ANP和BNP的上调以及SP1、SIRT1和SUMO1的下调。EPI可通过激活Sp1/SIRT1/SUMO1信号通路抑制TMAO诱导的心肌肥厚。
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Protective Role of (-)-Epicatechin on Trimethylamine-N-Oxide (TMAO)-Induced Cardiac Hypertrophy via SP1/SIRT1/SUMO1 Signaling Pathway.

(-)-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.

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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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