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      高脂血症患者血浆氧化三甲胺与血脂水平的相关性研究 Translated title: Correlation Between Plasma Trimethylamine N-Oxide and Lipid Levels in Hyperlipidemic Patients

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          Abstract

          目的

          探讨高脂血症患者机体血浆中氧化三甲胺(trimethylamine N-oxide, TMAO)水平和血脂水平的相关性。

          方法

          入选2019年3月–2021年3月就诊于新疆医科大学第一附属医院心脏中心的接受冠状动脉造影检查的患者130例。利用稳定同位素液相色谱/质谱法测定患者血浆中TMAO的水平。分析血浆TMAO水平和三酰甘油(triglycerides, TG)、总胆固醇(total cholesterol, TC)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-c)和低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-c)等血脂水平的相关性。

          结果

          高血脂患者血浆中TMAO的水平(μmol/L)高于血脂正常的患者(6.73±5.40 vs. 3.82±2.65),差异有统计学意义( P<0.05)。控制年龄和体质量指数的影响后,偏相关性分析结果显示,血浆中TMAO的水平与血浆TG( r=0.286, P<0.001)和HDL-c( r=−0.366, P<0.001)的水平有相关性。

          结论

          高脂血症患者血浆TMAO的水平和血脂水平具有相关性。

          Translated abstract

          Objective

          To investigate the correlation between the plasma levels of trimethylamine N-oxide (TMAO) and lipid levels in hyperlipidemic patients.

          Methods

          A total of 130 patients who received treatment and underwent coronary angiography at the Heart Center, the First Affiliated Hospital of Xinjiang Medical University between March 2019 and March 2021 were enrolled. Patients' plasma TMAO levels were determined by stable isotope liquid chromatography/mass spectrometry. The correlation between plasma TMAO levels and the levels of lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), was analyzed.

          Results

          Patients with hyperlipidemia had higher plasma TMAO levels (μmol/L) than patients without hyperlipidemia did (6.73±5.40 vs. 3.82±2.65), with the difference being statistically significant ( P<0.05). After controlling for the effects of age and body mass index, partial correlation analysis revealed that plasma TMAO levels were positively correlated with plasma TG ( r=0.286, P<0.001) and negatively correlated with HDL-C ( r=−0.366, P<0.001).

          Conclusion

          There is a correlation between plasma TMAO levels and lipid levels in hyperlipidemic patients.

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          Most cited references23

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          Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

          Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
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            Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

            Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.
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              Gut Microbiota and Cardiovascular Disease

              Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota–dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota–dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)—a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.
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                Author and article information

                Contributors
                Journal
                Sichuan Da Xue Xue Bao Yi Xue Ban
                Sichuan Da Xue Xue Bao Yi Xue Ban
                SCDXXBYXB
                Journal of Sichuan University (Medical Sciences)
                四川大学学报(医学版)编辑部 (中国四川 )
                1672-173X
                20 September 2023
                : 54
                : 5
                : 1030-1034
                Affiliations
                [1] 新疆医科大学第一附属医院 心脏中心 心脏外科 (乌鲁木齐 830000) Department of Cardiac Surgery, Heart Center, The First Affiliated Hospital of Xinjiang Medical University, Urumuqi 830000, China
                Author notes
                Article
                scdxxbyxb-54-5-1030
                10.12182/20230960109
                10579080
                37866964
                5c148c32-8539-4681-8bf7-270bddb0b5ba
                © 2023《四川大学学报(医学版)》编辑部 版权所有Copyright ©2023 Editorial Board of Journal of Sichuan University (Medical Sciences)

                开放获取 本文遵循知识共享署名—非商业性使用4.0国际许可协议(CC BY-NC 4.0),允许第三方对本刊发表的论文自由共享(即在任何媒介以任何形式复制、发行原文)、演绎(即修改、转换或以原文为基础进行创作),必须给出适当的署名,提供指向本文许可协议的链接,同时标明是否对原文作了修改;不得将本文用于商业目的。CC BY-NC 4.0许可协议访问 https://creativecommons.org/licenses/by-nc/4.0

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International license (CC BY-NC 4.0). In other words, the full-text content of the journal is made freely available for third-party users to copy and redistribute in any medium or format, and to remix, transform, and build upon the content of the journal. You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may not use the content of the journal for commercial purposes. For more information about the license, visit https://creativecommons.org/licenses/by-nc/4.0

                History
                : 24 May 2023
                Funding
                新疆维吾尔自治区自然科学基金青年项目(No.2020D01C256)资助
                Categories
                临床研究

                高脂血症,血浆氧化三甲胺,三酰甘油,总胆固醇,高密度脂蛋白胆固醇,低密度脂蛋白胆固醇,hyperlipidemia,trimethylamine n-oxide,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol

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