Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism

Article

关键词: LOW-DENSITY-LIPOPROTEIN;    CORONARY-ARTERY DISEASE;    ADHESION MOLECULES;    TISSUE FACTOR;    KAPPA-B;    LYSOPHOSPHATIDYLCHOLINE;    CHOLESTEROL;    PROGRESSION;    ANGIOGRAPHY;    EXPRESSION;   

DOI  :  10.1161/01.CIR.102.6.670

来源: SCIE

【 摘 要 】

Background-Triglyceride-rich lipoproteins (TGLs) are atherogenic. However, their cellular mechanisms remain largely unexplained. This study examined the effects of isolated remnant-like lipoprotein particles (RLPs) on the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and tissue factor (TF), proatherothrombogenic molecules, in cultured human endothelial cells. Methods and Results-RLPs were isolated from plasma of hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti-apoA-1 and anti-apoB-100 monoclonal antibodies. The incubation of cells with RLPs significantly upregulated mRNA and protein expression of these molecules. Total TGLs (d<1.006) and LDL had fewer or minimal effects on expression of these molecules compared with RLPs. RLPs increased intracellular oxidant levels, as assessed with an oxidant-sensitive probe. Combined incubation with ol-tocopherol or N-acetylcysteine, both antioxidants, suppressed RLP-induced increase in expression of these molecules. In patients with higher plasma levels of RLPs, plasma levels of soluble forms of ICAM-1 and VCAM-1 were significantly higher than in patients with lower RLP levels. Treatment with alpha-tocopherol for 1 month decreased levels of the soluble adhesion molecules concomitantly with an increase in resistance of RLPs to oxidative modification in patients with high RLP levels. Conclusions-RLPs upregulated endothelial expression of ICAM-1, VCAM-1, and TF, proatherothrombogenic molecules, partly through a redox-sensitive mechanism. RLPs may have an important role in atherothrombotic complications in hypertriglyceridemic patients.

【 授权许可】

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