Article

A major role for VCAM-1, but not ICAM-1, in early atherosclerosis

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto General Research Institute, Toronto, Ontario, Canada.
Journal of Clinical Investigation (Impact Factor: 13.22). 06/2001; 107(10):1255-62. DOI: 10.1172/JCI11871
Source: PubMed

ABSTRACT

VCAM-1 and ICAM-1 are endothelial adhesion molecules of the Ig gene superfamily that may participate in atherogenesis by promoting monocyte accumulation in the arterial intima. Both are expressed in regions predisposed to atherosclerosis and at the periphery of established lesions, while ICAM-1 is also expressed more broadly. To evaluate functions of VCAM-1 in chronic disease, we disrupted its fourth Ig domain, producing the murine Vcam1(D4D) allele. VCAM-1(D4D) mRNA and protein were reduced to 2-8% of wild-type allele (Vcam1(+)) levels but were sufficient to partially rescue the lethal phenotype of VCAM-1-null embryos. After crossing into the LDL receptor-null background, Vcam1(+/+) and Vcam1(D4D/D4D) paired littermates were generated from heterozygous intercrosses and fed a cholesterol-enriched diet for 8 weeks. The area of early atherosclerotic lesions in the aorta, quantified by en face oil red O staining, was reduced significantly in Vcam1(D4D/D4D) mice, although cholesterol levels, lipoprotein profiles, and numbers of circulating leukocytes were comparable to wild-type. In contrast, deficiency of ICAM-1 either alone or in combination with VCAM-1 deficiency did not alter nascent lesion formation. Therefore, although expression of both VCAM-1 and ICAM-1 is upregulated in atherosclerotic lesions, our data indicate that VCAM-1 plays a dominant role in the initiation of atherosclerosis.

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Available from: Su-Ning Zhu, Nov 18, 2015
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    • "Normally, intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular adhesion molecule-1 (VCAM-1, CD106), as important cell adhesion molecules, are members of the immunoglobulin superfamily of proteins and crucially mediates the adhesion of lymphocytes, monocytes, eosinophils and basophils to vascular endothelium (Hubbard and Rothlein, 2000; Barreiro et al., 2002; Yang et al., 2005). The interaction between ICAM-1 and VCAM-1 and their specific ligands expressed on microvascular endothedlial cells could be involved in cell adhesion (Collins et al., 2000; Cybulsky et al., 2001). ICAM-1 and VCAM-1 expressions are the consequence of stimulation by specific molecules including tumor necrosis factor-α (TNF), interleukin-1 (IL-1) and interferon-γ (IFN-γ) (Kume et al., 1992; Springer, 1994). "
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