Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice.
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.


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.
Goel
Reema
R
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201, USA.
Schrank
Benjamin R
BR
Arora
Shikha
S
Boylan
Brian
B
Fleming
Barbara
B
Miura
Hiroto
H
Newman
Peter J
PJ
Molthen
Robert C
RC
Newman
Debra K
DK
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D001854:Bone Marrow Cells / Q000378:metabolism; D004041:Dietary Fats; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012850:Sinus of Valsalva / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D004041:Dietary Fats; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011973:Receptors, LDL