Abstract
Trimethylamine N-oxide (TMAO) is a metabolite originated from bacterial metabolism of choline-rich foods. Evidence suggests an association between TMAO and atherosclerosis, but the relationship between TMAO and endothelial progenitor cells (EPCs) remains unclear. This study aimed to identify the relationship between TMAO concentrations, circulating EPCs, and endothelial function in patients with stable angina. Eighty-one stable angina subjects who underwent coronary angiography were enrolled. The circulating EPCs and flow-mediated vasodilation (FMD) were measured to evaluate endothelial function. Plasma TMAO and inflammatory markers, such as hsCRP and IL-1β, were determined. Furthermore, the effect of TMAO on EPCs was assessed in vitro. Patients with lower FMD had significantly decreased circulating EPCs, elevated TMAO, hsCRP, and IL-1β concentrations. Plasma TMAO levels were negatively correlated with circulating EPC numbers and the FMD, and positively correlated with hsCRP, IL-1β concentrations. In in vitro studies, incubation of TMAO in cultured EPCs promoted cellular inflammation, elevated oxidative stress, and suppressed EPC functions. Enhanced plasma TMAO levels were associated with reduced circulating EPCs numbers, endothelial dysfunction, and more adverse cardiovascular events. These findings provided evidence of TMAO’s toxicity on EPCs, and delivered new insight into the mechanism of TMAO-mediated atherosclerosis, which could be derived from TMAO-downregulated EPC functions.
Highlights
Trimethylamine N-oxide (TMAO) concentration at the same time[10]
Though Ke Y et al had recently conducted a study to show the association between circulating TMAO and vascular aging in 186 subjects, suggesting TMAO may deteriorate the endothelial function by increasing oxidative stress in human umbilical vein endothelial cells (HUVECs), they did not provide clinical information about the endothelial functions of enrolled patients[13]
During the median follow-up duration of 1.5 years, 16 cases (19.8%) of major adverse cardiovascular event (MACE) occurred after Coronary angiography (CAG), including 14 cases (17.3%) of target vessel revascularization and 2 cases (2.5%) of nonfatal myocardial infarction (MI)
Summary
TMAO concentration at the same time[10]. In human umbilical vein endothelial cells (HUVECs), TMAO has been suggested to be associated with endothelial dysfunction[5], an early event in the development of atherosclerosis[11]. Though Ke Y et al had recently conducted a study to show the association between circulating TMAO and vascular aging in 186 subjects, suggesting TMAO may deteriorate the endothelial function by increasing oxidative stress in HUVECs, they did not provide clinical information about the endothelial functions of enrolled patients[13]. We hypothesized that an enhanced TMAO level might provoke inflammation and induce changes in the numbers and function of EPCs, contributing to endothelial dysfunction. In this single-center translational study, we investigated the association between TMAO, circulating EPCs, and endothelial function in patients with stable angina. To confirm the causal relationship between TMAO and endothelial dysfunction, we treated human EPCs with different concentrations of TMAO
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