ABSTRACT
Cell adhesion molecules, by mediating the recruitment of circulating leukocytes to the blood vessel wall and their subsequent adherence and transendothelial migration, play critical roles in all stages of atherosclerotic lesion development. Various infl ammatory stimuli induce expression of adhesion molecules. Th is chapter highlights the direct functions of apolipoproteins, surface constituents of plasma circulating lipoproteins, in monocyte activation and vascular endothelium dysfunction. Apolipoproteins regulate lipoprotein metabolism, and their dysregulation closely associates with hypercholesterolemia, hypertriglyceridemia and insulin resistance, dysmetabolic states that predispose patients at elevated
risk for coronary heart disease. Recent preclinical studies by our group and others have demonstrated that apolipoprotein C-III, alone or as a component of plasma apoB lipoproteins, promotes monocyte adhesion to vascular endothelial cells via activation of cellular adhesion molecules. Apolipoprotein C-III also induces the activation of nuclear factor κB, a pleiotropic transcription factor that regulates expression of many pro-infl ammatory molecules including cytokines and their receptors. Besides apolipoprotein C-III, emerging evidence suggests that other apolipoproteins such as lipoprotein(a), apolipoprotein E, and apolipoprotein A-I also mediate monocyte adhesion to the vascular endothelium, in addition to their regulatory functions in lipoprotein metabolism. Th ese exciting fi ndings, therefore, provide a direct link between dyslipidemia and monocyte activation and endothelial cell dysfunction.
