Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
Sci Rep. 2019 Mar 12;9(1):4249. doi: 10.1038/s41598-019-40638-y.
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.
三甲基胺 N-氧化物（TMAO）是一种来源于富含胆碱的食物的细菌代谢产物。有证据表明 TMAO 与动脉粥样硬化之间存在关联，但 TMAO 与内皮祖细胞（EPCs）之间的关系尚不清楚。本研究旨在确定稳定型心绞痛患者 TMAO 浓度、循环 EPCs 和内皮功能之间的关系。共纳入 81 例接受冠状动脉造影的稳定型心绞痛患者。测量循环 EPCs 和血流介导的血管扩张（FMD）以评估内皮功能。测定血浆 TMAO 和炎症标志物，如 hsCRP 和 IL-1β。此外，还评估了 TMAO 对 EPCs 的体外作用。FMD 较低的患者循环 EPCs 明显减少，TMAO、hsCRP 和 IL-1β 浓度升高。血浆 TMAO 水平与循环 EPC 数量和 FMD 呈负相关，与 hsCRP、IL-1β 浓度呈正相关。在体外研究中，TMAO 在培养的 EPCs 中孵育可促进细胞炎症、增加氧化应激，并抑制 EPC 功能。增强的血浆 TMAO 水平与循环 EPCs 数量减少、内皮功能障碍和更多不良心血管事件相关。这些发现提供了 TMAO 对 EPCs 毒性的证据，并深入了解了 TMAO 介导的动脉粥样硬化的机制，这可能源于 TMAO 下调 EPC 功能。
