Title

Site-Specific Effects of PECAM-1 on Atherosclerosis in LDL Receptor-Deficient Mice

Document Type

Article

Language

eng

Format of Original

7 p.

Publication Date

2008

Publisher

American Heart Association

Source Publication

Arteriosclerois, Thrombosis, and Vascular Biology

Source ISSN

1079-5642

Original Item ID

doi: 10.1161/ATVBAHA.108.172270

Abstract

Objective—Atherosclerosis is a vascular disease that involves lesion formation at sites of disturbed flow under the influence of genetic and environmental factors. Endothelial expression of adhesion molecules that enable infiltration of immune cells is important for lesion development. Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) is an adhesion and signaling receptor expressed by many cells involved in atherosclerotic lesion development. PECAM-1 transduces signals required for proinflammatory adhesion molecule expression at atherosusceptible sites; thus, it is predicted to be proatherosclerotic. PECAM-1 also inhibits inflammatory responses, on which basis it is predicted to be atheroprotective.

Methods and Results—We evaluated herein the effect of PECAM-1 deficiency on development of atherosclerosis in LDL receptor– deficient mice. We found that PECAM-1 has both proatherosclerotic and atheroprotective effects, but that the former dominate in the inner curvature of the aortic arch whereas the latter dominate in the aortic sinus, branching arteries, and descending aorta. Endothelial cell expression of PECAM-1 was sufficient for its atheroprotective effects in the aortic sinus but not in the descending aorta, where the atheroprotective effects of PECAM-1 also required its expression on bone marrow–derived cells.

Conclusion—We conclude that PECAM-1 influences initiation and progression of atherosclerosis both positively and negatively, and that it does so in a site-specific manner. (Arterioscler Thromb Vasc Biol. 2008;28:1996-2002)

Comments

Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 28, No. 11 (July 2008): 1996-2002. DOI.