Remnant Lipoproteins Induce Proatherothrombogenic Molecules in Endothelial Cells Through a Redox-Sensitive Mechanism

Abstract

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 α-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 α-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.