Platelet P-selectin facilitates atherosclerotic lesion development

Blood. 2003 Apr 1;101(7):2661-6. doi: 10.1182/blood-2002-07-2209. Epub 2002 Dec 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics
  • Arteriosclerosis / etiology*
  • Arteriosclerosis / pathology
  • Blood Platelets / chemistry*
  • Bone Marrow Transplantation
  • Cell Movement
  • Endothelium, Vascular / chemistry*
  • Endothelium, Vascular / cytology
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Smooth Muscle / pathology
  • P-Selectin / blood
  • P-Selectin / genetics
  • P-Selectin / physiology*
  • Solubility


  • Apolipoproteins E
  • P-Selectin