This Article Full Text Full Text (PDF) All Versions of this Article: 28/11/1996    most recent ATVBAHA.108.172270v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goel, R. Articles by Newman, D. K. Search for Related Content PubMed PubMed Citation Articles by Goel, R. Articles by Newman, D. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Genetics Home Reference Related Collections Related Article

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1996.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

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

Reema Goel; Benjamin R. Schrank; Shikha Arora; Brian Boylan; Barbara Fleming; Hiroto Miura; Peter J. Newman; Robert C. Molthen; Debra K. Newman

From the Blood Research Institute (R.G., B.R.S., S.A., B.B., B.F., P.J.N., D.K.N.), BloodCenter of Wisconsin, Milwaukee; the Department of Veterans Affairs (R.C.M.), Zablocki VA Medical Center, Milwaukee, Wisconsin; the Cardiovascular Center (H.M.) and the Departments of Medicine (H.M., R.C.M.), Pharmacology and Toxicology (P.J.N., D.K.N.), Cell Biology, Neurobiology, and Anatomy (P.J.N.), and Microbiology and Molecular Genetics (D.K.N.), Medical College of Wisconsin, Milwaukee.

Correspondence to Debra Newman, PhD, Blood Research Institute, BloodCenter of Wisconsin, P.O. Box 2178, Milwaukee, WI 53201. E-mail debra.newman{at}bcw.edu

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.

Key Words: PECAM-1 • CD31 • atherosclerosis • LDL-receptor • inflammation

Related Article:

Morphing the Topography of Atherosclerosis: An Unexpected Role for PECAM-1

Myron I. Cybulsky
Arterioscler. Thromb. Vasc. Biol. 2008 28: 1887-1889. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				Z. Chen and E. Tzima PECAM-1 Is Necessary for Flow-Induced Vascular Remodeling Arterioscler. Thromb. Vasc. Biol., July 1, 2009; 29(7): 1067 - 1073. [Abstract] [Full Text] [PDF]