Platelet P-selectin facilitates atherosclerotic lesion development.
P-selectin is an adhesion molecule expressed on activated platelets and endothelium. It is known to play an important role in atherosclerosis. P-selectin also circulates in plasma in a soluble form (sP-selectin), which induces procoagulant microparticle formation. We investigated the role of platelet versus endothelial P-selectin in generating sP-selectin and in the formation of atherosclerotic lesions in the apolipoprotein E (apoE)-deficient mouse model. For this we transplanted apoE(-/-)P-selectin(-/-) and apoE(-/-)P-selectin(+/+) lethally irradiated mice with bone marrow of either genotype. Seven months after transplantation, we determined from the chimeric animals that the majority of circulating sP-selectin was of endothelial origin. Thus, in atherosclerosis, the procoagulant sP-selectin reflects endothelial rather than platelet activation. We found that endothelial P-selectin was crucial for the promotion of atherosclerotic lesion growth because in its absence only relatively small lesions developed. However, platelet P-selectin also contributed to the lesion development because lesions in wild-type recipients receiving transplants with wild-type platelets were 30% larger than those receiving P-selectin-deficient platelets (P <.008) and were more frequently calcified (80% versus 44%). In comparison with P-selectin wild-type animals, absence of either endothelial or platelet P-selectin inhibited migration of smooth muscle cells into the lesion. Thus, in addition to endothelium, platelets and their P-selectin also actively promote advanced atherosclerotic lesion development.
Burger
Peter C
PC
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Wagner
Denisa D
DD
D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D001792:Blood Platelets / Q000737:chemistry*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D019007:P-Selectin / Q000097:blood / Q000235:genetics / Q000502:physiology*; D012995:Solubility
D001057:Apolipoproteins E; D019007:P-Selectin