Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion.
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.
['Ma|GuoHua|G|', 'Pan|Bing|B|', 'Chen|Yue|Y|', 'Guo|CaiXia|C|', 'Zhao|MingMing|M|', 'Zheng|LeMin|L|', 'Chen|BuXing|B|']
D050197:Atherosclerosis D002448:Cell Adhesion D002478:Cells, Cultured D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D008744:Methylamines D009000:Monocytes D016328:NF-kappa B D011493:Protein Kinase C D015398:Signal Transduction D019010:Vascular Cell Adhesion Molecule-1
TMAO Atherosclerosis Endothelial dysfunction PKC/ NF-κB