Platelet P-selectin facilitates atherosclerotic lesion development

Peter C. Burger, Denisa D. Wagner

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2661-2666
Number of pages6
JournalBlood
Volume101
Issue number7
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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