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Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion

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机构: [1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,Beijing 100050,Peoples R China [2]Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China [3]Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed, Beijing 100191, Peoples R China [4]Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China [5]Shantou Univ, Med Coll, Shantou 515041, Peoples R China
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关键词: KAPPA-B ACTIVATION PROGNOSTIC VALUE GUT MICROBIOTA PKC-ALPHA DYSFUNCTION METABOLISM CELLS PHOSPHATIDYLCHOLINE EXPRESSION CARNITINE

摘要:
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 HUVECsmigration in transwellmigration 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-kB. 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-kB/VCAM-1.

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基金编号: 81170101 81370235 81570321 81172500 81450012

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 细胞生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 4 区 细胞生物学
第一作者:
第一作者机构: [1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,Beijing 100050,Peoples R China [5]Shantou Univ, Med Coll, Shantou 515041, Peoples R China
通讯作者:
通讯机构: [1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,Beijing 100050,Peoples R China [*1]Capital Med Univ, Beijing Tian Tan Hosp, Dept Cardiol, Beijing 100050, Peoples R China [2]Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China [*2]Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China [3]Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed, Beijing 100191, Peoples R China [*3]Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed, Beijing 100191, Peoples R China [4]Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China [*4]Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China
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