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Molecules affecting atherosclerotic disease progression

VCAM-1 has a dominant role in initiation of atherosclerosis but macrophage MMP-1 activity seems to limit the progression of disease.

Tudor Toma(ttoma@mail.dntis.ro)

In May 15 Journal of Clinical Investigation two papers provide further details of the mechanisms of initiation and progression of atherosclerotic lesions.

Cybulsky et al from the University of Toronto, Canada show that VCAM-1 and not ICAM-1 plays a dominant role in the initiation of atherosclerosis. VCAM-1 and ICAM-1 are endothelial adhesion molecules of the Ig gene superfamily.

They manipulated the Ig domain and obtained a VCAM-1 deficient mouse. When fed on a cholesterol-enriched diet, mice VCAM-1 deficient showed a reduced area of early atherosclerotic lesions in the aorta, 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 did not alter lesion formation (J Clin Invest 2001, 107:1255-1262).

In a second paper, Lemaître et al from the Columbia University College of Physicians and Surgeons, New York demonstrate that remodelling...

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