Adhesion of Monocytes to Arterial Endothelium and Initiation of Atherosclerosis Are Critically Dependent on Vascular Cell Adhesion Molecule-1 Gene Dosage

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 21; no. 10; pp. 1662 - 1667
• Main Authors: Dansky, Hayes M, Barlow, Courtenay B, Lominska, Chris, Sikes, John L, Kao, Catherine, Weinsaft, Jonathan, Cybulsky, Myron I, Smith, Jonathan D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.10.2001; Hagerstown, MD Lippincott
• Subjects: Animals; Aorta - metabolism; Apolipoproteins E - genetics; Arteriosclerosis - etiology; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion; Endothelium, Vascular - physiology; Female; Gene Dosage; Gene Targeting; Hypercholesterolemia - etiology; Leukocyte Count; Male; Medical sciences; Mice; Mice, Knockout; Monocytes - physiology; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - physiology; Vascular cell adhesion molecule 1; Pathogenesis; Transgenic animal; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Genetic determinism; Vascular disease; Apolipoprotein E; Atherosclerosis; Aorta; Dyslipemia; Vascular wall; Gene dosage; Monocyte; Deficiency; Rodentia; Metabolic diseases; Exploration; Adhesion; Genetic disease; Endothelium; Vertebrata; Mammalia; Hypercholesterolemia; Mouse
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/hq1001.096625

Vascular cell adhesion molecule-1 (VCAM-1/ Vcam1) is a cytokine-inducible member of the immunoglobulin gene superfamily that is expressed by arterial endothelial cells in regions predisposed to atherosclerosis and at borders of atherosclerotic plaques. To determine whether VCAM-1 expression regulates atherosclerotic lesion formation, we crossed Vcam1 domain 4–deficient (D4D) mice, which partially circumvent the embryonic lethality of Vcam1 null mice, with apolipoprotein E null (Apoe) mice, which spontaneously develop hypercholesterolemia and atherosclerosis. In the Apoe background, mice homozygous for the Vcam1 D4D allele had markedly reduced arterial VCAM-1 expression, monocyte adherence in the aortic root, and fatty streak formation. Heterozygous Vcam1 D4D mice revealed a Vcam1 gene-dosage effect and had intermediate, yet significant, reductions in these parameters. Our data demonstrate that VCAM-1 plays a pivotal role in the initiation of atherosclerosis in Apoe mice.