Department of Cardiology and Vascular Medicine, General Hospital Dr. Soetomo, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.
Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.
Biomol Biomed. 2023 Nov 3;23(6):936-948. doi: 10.17305/bb.2023.8893.
Current research supports the evidence that the gut microbiome (GM), which consist of gut microbiota and their biologically active metabolites, is associated with atherosclerosis development. Trimethylamine-N-oxide (TMAO), a metabolite produced by the GM through trimethylamine (TMA) oxidation, significantly enhances the formation and vulnerability of atherosclerotic plaques. TMAO promotes inflammation and oxidative stress in endothelial cells, leading to vascular dysfunction and plaque formation. Dimethyl-1-butanol (DMB), iodomethylcholine (IMC) and fluoromethylcholine (FMC) have been recognized for their ability to reduce plasma TMAO by inhibiting trimethylamine lyase, a bacterial enzyme involved in the choline cleavage anaerobic process, thus reducing TMA formation. Conversely, indole-3-carbinol (I3C) and trigonelline inhibit TMA oxidation by inhibiting flavin-containing monooxygenase-3 (FMO3), resulting in reduced plasma TMAO. The combined use of inhibitors of choline trimethylamine lyase and flavin-containing monooxygenase-3 could provide novel therapeutic strategies for cardiovascular disease prevention by stabilizing existing atherosclerotic plaques. This review aims to present the current evidence of the roles of TMA/TMAO in atherosclerosis as well as its potential therapeutic prevention aspects.
目前的研究支持了这样的证据，即肠道微生物组（GM），由肠道微生物及其生物活性代谢物组成，与动脉粥样硬化的发展有关。三甲胺 N-氧化物（TMAO）是 GM 通过三甲胺（TMA）氧化产生的一种代谢物，显著增强了动脉粥样硬化斑块的形成和脆弱性。TMAO 促进内皮细胞的炎症和氧化应激，导致血管功能障碍和斑块形成。二甲-1-丁醇（DMB）、碘代甲基胆碱（IMC）和氟代甲基胆碱（FMC）已被证明能够通过抑制参与胆碱裂解厌氧过程的细菌酶三甲基胺裂解酶来降低血浆 TMAO，从而减少 TMA 的形成。相反，吲哚-3-甲醇（I3C）和三叶草碱通过抑制黄素单加氧酶-3（FMO3）抑制 TMA 氧化，导致血浆 TMAO 减少。胆碱三甲基胺裂解酶和黄素单加氧酶-3 的抑制剂联合使用，可能通过稳定现有的动脉粥样硬化斑块，为心血管疾病的预防提供新的治疗策略。本综述旨在介绍 TMA/TMAO 在动脉粥样硬化中的作用及其潜在的治疗预防方面的最新证据。
