Burger Peter C, Wagner Denisa D
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
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.
P-选择素是一种在活化血小板和内皮细胞上表达的黏附分子。已知它在动脉粥样硬化中起重要作用。P-选择素也以可溶性形式（sP-选择素）在血浆中循环，可诱导促凝微粒形成。我们在载脂蛋白E（apoE）缺陷小鼠模型中研究了血小板与内皮P-选择素在生成sP-选择素及动脉粥样硬化病变形成中的作用。为此，我们用两种基因型的骨髓移植apoE(-/-)P-选择素(-/-)和apoE(-/-)P-选择素(+/+)经致死性照射的小鼠。移植7个月后，我们从嵌合动物中确定，循环中的大多数sP-选择素来源于内皮。因此，在动脉粥样硬化中，促凝的sP-选择素反映的是内皮而非血小板的活化。我们发现内皮P-选择素对促进动脉粥样硬化病变生长至关重要，因为在其缺失时仅形成相对较小的病变。然而，血小板P-选择素也对病变发展有贡献，因为接受野生型血小板移植的野生型受体中的病变比接受P-选择素缺陷血小板的受体中的病变大30%（P<.008），且钙化更频繁（80%对44%）。与P-选择素野生型动物相比，内皮或血小板P-选择素的缺失均抑制平滑肌细胞向病变内迁移。因此，除了内皮，血小板及其P-选择素也积极促进晚期动脉粥样硬化病变的发展。
