Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 2008 Nov;28(11):1996-2002
Date
08/02/2008Pubmed ID
18669884Pubmed Central ID
PMC3013511DOI
10.1161/ATVBAHA.108.172270Scopus ID
2-s2.0-55449106035 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
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.
CONCLUSIONS: 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.
Author List
Goel R, Schrank BR, Arora S, Boylan B, Fleming B, Miura H, Newman PJ, Molthen RC, Newman DKAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinDebra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAorta, Thoracic
Atherosclerosis
Bone Marrow Cells
Dietary Fats
Disease Models, Animal
Disease Progression
Endothelial Cells
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Platelet Endothelial Cell Adhesion Molecule-1
Receptors, LDL
Sinus of Valsalva
Time Factors
