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.
Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China.|Medical College of Shantou University, Shantou 515041, China.
GuoHua
G
Ma
Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
Bing
B
Pan
Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
Yue
Y
Chen
Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China.
CaiXia
C
Guo
Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
MingMing
M
Zhao
Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China chbux@126.com zhengl@bjmu.edu.cn.
LeMin
L
Zheng
Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China chbux@126.com zhengl@bjmu.edu.cn.
BuXing
B
Chen
D050197:Atherosclerosis / Q000097:blood* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008744:Methylamines / Q000097:blood*; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D008744:Methylamines; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D011493:Protein Kinase C; C005855:trimethyloxamine
Atherosclerosis; Endothelial dysfunction; PKC/ NF-κB; TMAO