Platelet factor 4 mediates vascular smooth muscle cell injury responses
Platelet factor 4 mediates vascular smooth muscle cell injury responses
复制标题
DOI：
10.1182/blood-2012-09-454710
复制
发表时间：
2013-05-23
期刊：
影响因子：
20.3
通讯作者：
Morrell, Craig N.
中科院分区：
文献类型：
--
作者：
Shi, Guanfang;Field, David J.;Morrell, Craig N.
活化的血小板释放许多炎症分子，在加速血管炎症中起重要作用。关于血小板和血小板衍生的介质与内皮细胞和白细胞的相互作用已经知道很多，但是很少有研究检查血小板对血管壁成分的影响。血管平滑肌细胞（VSMC）响应于损伤而经历表型变化，包括炎性分子的产生、细胞增殖、细胞迁移和分化标志物表达的下降。在这项研究中，我们证明，血小板衍生的趋化因子血小板因子4（PF 4/CXCL 4）刺激VSMC损伤反应在体外和体内的小鼠颈动脉结扎模型。PF 4驱动VSMC炎性表型，包括分化标志物下降、细胞因子产生增加和细胞增殖。我们还表明，PF 4的影响是介导的，在一定程度上，通过增加转录因子Kruppel样因子4的表达。我们的数据表明，在体外和体内的VSMC损伤反应中血小板和PF 4的重要机制作用。
Activated platelets release many inflammatory molecules with important roles in accelerating vascular inflammation. Much is known about platelet and platelet-derived mediator interactions with endothelial cells and leukocytes, but few studies have examined the effects of platelets on components of the vascular wall. Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to injury including the production of inflammatory molecules, cell proliferation, cell migration, and a decline in the expression of differentiation markers. In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model. PF4 drives a VSMC inflammatory phenotype including a decline in differentiation markers, increased cytokine production, and cell proliferation. We also demonstrate that PF4 effects are mediated, in part, through increased expression of the transcription factor Kruppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.