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

Background-Triglyceride-rich lipoproteins (TGLs) are atherogenic. However, their cellular mechanisms remain largely unexplained. This study examined t he effects of isolated remnant-like lipoprotein particles (RLPs) on the exp ression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesi on molecule-1 (VCAM-1), and tissue factor (TF), proatherothrombogenic molec ules, 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-a poB-100 monoclonal antibodies. The incubation of cells with RLPs significan tly upregulated mRNA and protein expression of these molecules. Total TGLs (d<1.006) and LDL had fewer or minimal effects on expression of these molec ules compared with RLPs. RLPs increased intracellular oxidant levels, as as sessed with an oxidant-sensitive probe. Combined incubation with ol-tocophe rol 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 significant ly higher than in patients with lower RLP levels. Treatment with alpha-toco pherol for 1 month decreased levels of the soluble adhesion molecules conco mitantly with an increase in resistance of RLPs to oxidative modification i n patients with high RLP levels. Conclusions-RLPs upregulated endothelial expression of ICAM-1, VCAM-1, and TF, proatherothrombogenic molecules, partly through a redox-sensitive mecha nism. RLPs may have an important role in atherothrombotic complications in hypertriglyceridemic patients.