Platelet P-selectin facilitates atherosclerotic lesion development
Platelet P-selectin facilitates atherosclerotic lesion development
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DOI：
10.1182/blood-2002-07-2209
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发表时间：
2003-04-01
期刊：
影响因子：
20.3
通讯作者：
Wagner, DD
中科院分区：
文献类型：
--
作者：
Burger, PC;Wagner, DD
P-选择素是一种粘附分子，表达于活化的血小板和内皮细胞上。已知它在动脉粥样硬化中起重要作用。P-选择素还以可溶形式（sP-选择素）在血浆中循环，其诱导促凝血微粒形成。我们研究了血小板与内皮P-选择素在产生sP-选择素和载脂蛋白E（apoE）缺陷小鼠模型中动脉粥样硬化病变形成中的作用。为此，我们将apoE（-/-）P-选择素（-/-）和apoE（-/-）P-选择素（+/+）致死辐射小鼠的骨髓移植给任一基因型。移植后7个月，我们从嵌合体动物中确定了大部分循环中的sP-选择素是内皮来源的。因此，在动脉粥样硬化中，促凝血sP-选择素反映内皮而不是血小板活化。我们发现，内皮P-选择素是至关重要的促进动脉粥样硬化病变的生长，因为在它的情况下，只有相对较小的病变发展。然而，血小板P-选择素也促进了病变的发展，因为接受野生型血小板移植的野生型受者的病变比接受P-选择素缺陷型血小板移植的受者大30%（P
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