Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Blood. 2013 May 23;121(21):4417-27. doi: 10.1182/blood-2012-09-454710. Epub 2013 Apr 8.
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 Krüppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.
活化的血小板释放许多具有加速血管炎症作用的炎症分子。人们对血小板与内皮细胞和白细胞之间的相互作用以及血小板衍生的介质有了很多了解，但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）在受到损伤时会发生表型变化，包括炎症分子的产生、细胞增殖、细胞迁移以及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（PF4/CXCL4）在体外和体内的小鼠颈动脉结扎模型中均能刺激 VSMC 的损伤反应。PF4 驱动 VSMC 的炎症表型，包括分化标志物的下降、细胞因子产生的增加和细胞增殖。我们还证明，PF4 的作用部分是通过转录因子 Krüppel-like factor 4 的表达增加来介导的。我们的数据表明，血小板和 PF4 在 VSMC 的损伤反应中具有重要的机制作用，无论是在体外还是体内。
