Baker IDI Heart and Diabetes Institute, Commercial Rd, Melbourne 3004, Australia.
Curr Pharm Des. 2010;16(37):4113-8. doi: 10.2174/138161210794519192.
Inflammation plays a fundamental role in many chronic diseases, including atherosclerosis associated cardiovascular disease. Adhesion of immune cells plays a critical role in the inflammatory response and indeed the pathophysiology of inflammatory related diseases. P-selectin is an inflammatory adhesion molecule, enabling the recruitment of leukocytes to the endothelium and to activated platelets involved with the growing thrombus. P-selectin is critical in the progression of atherosclerosis as evidenced by knockout animal models where P-selectin knockout mice crossed with apoE deficient mice exhibit significantly reduced atherosclerosis and leukocyte recruitment in the plaque. A soluble form of P-selectin also exists, which may have pro-atherogenic and pro-thrombotic effects. Thus targeting of P-selectin remains a strong clinical candidate for developing novel therapeutic strategies in inflammatory diseases. This review will discuss the role of P-selectin and describe the function of P-selectin antagonists as clinical targets.
炎症在许多慢性疾病中起着根本性的作用，包括与动脉粥样硬化相关的心血管疾病。免疫细胞的黏附在炎症反应中起着关键作用，实际上在炎症相关疾病的病理生理学中也是如此。P 选择素是一种炎症黏附分子，能够将白细胞募集到血管内皮细胞，并募集到与正在生长的血栓有关的活化血小板。P 选择素在动脉粥样硬化的进展中起着至关重要的作用，这一点可以从基因敲除动物模型中得到证明，在这些模型中，P 选择素基因敲除小鼠与载脂蛋白 E 缺陷小鼠杂交后，动脉粥样硬化斑块中的动脉粥样硬化和白细胞募集明显减少。P 选择素也存在可溶性形式，它可能具有促动脉粥样硬化和促血栓形成的作用。因此，针对 P 选择素仍然是开发炎症性疾病新治疗策略的一个强有力的临床候选靶点。本综述将讨论 P 选择素的作用，并描述 P 选择素拮抗剂作为临床靶点的功能。
