(Circulation. 2000;102:670.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Remnant Lipoproteins Induce Proatherothrombogenic Molecules in Endothelial Cells Through a Redox-Sensitive Mechanism
From the Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto City, Japan.
Correspondence to Kiyotaka Kugiyama, MD, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City, 860-8556 Japan. E-mail kiyo{at}gpo.kumamoto-u.ac.jp
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 
-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 -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.
Key Words: lipoproteins • endothelium • cell adhesion molecules • antioxidants • atherosclerosis
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