Choline and trimethylamine N-oxide impair metabolic activation of and platelet response to clopidogrel through activation of the NOX/ROS/Nrf2/CES1 pathway

Ge, Peng-Xin; Tai, Ting; Jiang, Liang; Ji, Jin-Zi; Mi, Qiong‐Yu; Zhu, Ting; Li, Yi-Fei; Xie, Hong‐Guang

doi:10.1016/j.jtha.2022.10.010

Cited by 4 publications

(2 citation statements)

References 52 publications

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“…Moreover, TMAO impairs cholesterol efflux mechanisms, preventing the removal of cholesterol from macrophages and promoting their transformation into foam cells [ 50 ]. TMAO induces platelet activation and hyperactivity and can reduce the efficacy of clopidogrel [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Benefits of Taurisolo in Diabetic Patients with Peripheral Artery Disease

Amato,

Novellino,

Morlando

et al. 2024

JCDD

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Trimethyl-N-oxide (TMAO) has been linked to peripheral artery disease (PAD). TaurisoloⓇ is a natural, balanced phytocomplex containing resveratrol, quercetin, catechins, procianidins, gallic acid, and caffeic acid. Numerous studies have shown that TaurisoloⓇ reduces the damage of TMAO and exerts a protective effect on endothelial cells (ECs). The aim of this randomized, double-blind, single-center study was to evaluate the effects of TaurisoloⓇ on claudication in patients with PAD (Rutheford grade I, category II, Fontaine Classification: Stage IIA, American Medical Association Whole Person Impairment Classification: Class 0—WPI 0%) in two parallel groups of 31 patients. The primary outcomes were an increase in the pain-free walking distance and the ankle/brachial pressure index at the beginning and at the end of the treatment with Taurisolo. The secondary endpoint was the serum TMAO changes. The claudication distance improved by 14.1% in the Taurisolo group and by 2.0% in the placebo group, while the maximal distance increased by 15.8% and 0.6% only, respectively (both p < 0.05). The TMAO plasma levels decreased from 3.97 ± 2.13 micromole/L to 0.87 ± 0.48 (p < 0.0001) in the treated group. All these changes were highly significant both in univariate mixed models as well as in the adjusted model. Ultimately, TaurisoloⓇ might be an effective intervention to ameliorate intermittent claudication.

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Section: Discussionmentioning

confidence: 99%

Benefits of Taurisolo in Diabetic Patients with Peripheral Artery Disease

Amato,

Novellino,

Morlando

et al. 2024

JCDD

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“…While it has been shown that prothrombotic and pro-atherothrombotic effects are important mechanisms of TMAO’s detrimental impact, there is evidence to suggest that the correlation between TMAO and platelet reactivity is not particularly strong [ 69 , 70 ]. Furthermore, studies have demonstrated that choline and TMAO activate the NOX/ROS/Nrf2/CES1 pathway, which decreases the formation of clopidogrel active metabolite and impairs platelet response to clopidogrel [ 71 ]. Despite this, elevated TMAO levels have been significantly associated with coronary CVD in patients who received antiplatelet therapy for CVD [ 72 ].…”

Section: Introductionmentioning

confidence: 99%

Association between Intestinal Microecological Changes and Atherothrombosis

et al. 2023

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Atherosclerosis (AS) is a chronic inflammatory disease of large- and medium-sized arteries that causes ischemic heart disease, strokes, and peripheral vascular disease, collectively called cardiovascular disease (CVD), and is the leading cause of CVD resulting in a high rate of mortality in the population. AS is pathological by plaque development, which is caused by lipid infiltration in the vessel wall, endothelial dysfunction, and chronic low-grade inflammation. Recently, more and more scholars have paid attention to the importance of intestinal microecological disorders in the occurrence and development of AS. Intestinal G-bacterial cell wall lipopolysaccharide (LPS) and bacterial metabolites, such as oxidized trimethylamine (TMAO) and short-chain fatty acids (SCFAs), are involved in the development of AS by affecting the inflammatory response, lipid metabolism, and blood pressure regulation of the body. Additionally, intestinal microecology promotes the progression of AS by interfering with the normal bile acid metabolism of the body. In this review, we summarize the research on the correlation between maintaining a dynamic balance of intestinal microecology and AS, which may be potentially helpful for the treatment of AS.

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