Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion
Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion
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三甲胺 N-氧化物在动脉粥样硬化形成中：损害内皮自我修复能力并增强单核细胞粘附
DOI：
10.1042/bsr20160244
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发表时间：
2017-04-01
影响因子：
4
通讯作者：
Chen, BuXing
中科院分区：
文献类型：
--
作者：
Ma, GuoHua;Pan, Bing;Chen, BuXing
已有多项研究报道，血浆中高水平的三甲胺氮氧化物(TMAO)与动脉粥样硬化的发生有很强的相关性。然而，这种关联背后的确切机制尚不清楚。在本研究中，我们试图探讨TMAO对内皮功能障碍的影响。经TMAO处理后，人脐静脉内皮细胞(HUVECs)的细胞增殖和与细胞外基质(ECM)的黏附与对照组相比明显受损。同样，TMAO明显抑制人脐静脉内皮细胞跨膜迁移和伤口愈合实验。此外，我们还发现TMAO上调血管细胞黏附分子-1的表达，促进单核细胞黏附，活化的蛋白激酶C和p-NF-κB。有趣的是，TMAO刺激的血管细胞黏附分子-1表达和单核细胞黏附被PKC抑制剂抑制。这些结果表明，TMAO通过加速内皮功能障碍，包括降低内皮自我修复和增加单核细胞黏附，促进动脉粥样硬化的早期病理过程。此外，氧化三甲胺诱导的单核细胞黏附作用部分归因于PKC/NF-κB/VCAM1的激活。
Several studies have reported a strong association between high plasma level of trimethylamine N-oxide (TMAO) and atherosclerosis development. However, the exact mechanism underlying this correlation is unknown. In the present study, we try to explore the impact of TMAO on endothelial dysfunction. After TMAO treatment, human umbilical vein endothelial cells (HUVECs) showed significant impairment in cellular proliferation and HUVECs-extracellular matrix (ECM) adhesion compared with control. Likewise, TMAO markedly suppressed HUVECs migration in transwell migration assay and wound healing assay. In addition, we found TMAO up-regulated vascular cell adhesion molecule-1 (VCAM-1) expression, promoted monocyte adherence, activated protein kinase C (PKC) and p-NF-κB. Interestingly, TMAO-stimulated VCAM-1 expression and monocyte adherence were diminished by PKC inhibitor. These results demonstrate that TMAO promotes early pathological process of atherosclerosis by accelerating endothelial dysfunction, including decreasing endothelial self-repair and increasing monocyte adhesion. Furthermore, TMAO-induced monocyte adhesion is partly attributable to activation of PKC/NF-κB/VCAM-1.