Department of Thoracic and Cardiovascular Surgery, School of Medicine, Pusan National University, Busan, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jun 4;396(3):748-54. doi: 10.1016/j.bbrc.2010.05.009. Epub 2010 May 6.
Expression of PAR, the thrombin receptor, is elevated in smooth muscle cell-rich areas in atherosclerotic plaques, where the cells change to proinflammatory or synthetic phenotype. In this study we investigated whether thrombin promotes a proinflammatory phenotype in vascular smooth muscle cell (VSMC), characterized by increased cytokine and chemokine synthesis. Thrombin not only elevated transcripts for IL-6, CXCL8, and CCL11 genes but also enhanced release of IL-6 and CXCL8 protein from human aortic smooth muscle cell (HAoSMC). Thrombin activated Akt, PKC and MAPK in HAoSMC, and thrombin-mediated expression of IL-6 and CXCL8 was significantly inhibited by LY294002, AKT IV, RO318220, and GF109203X as well as by diphenyleneiodium at the messenger RNA and the protein levels. SB202129 and U0126 also significantly attenuated thrombin-mediated release of IL-6 and CXCL8 proteins from HAoSMC. These results indicate that thrombin promotes proinflammatory phenotype in human VSMC and that PI3K, Akt, PKC, NADPH oxidase, and MAPK are involved in that process. We propose that activation VSMC in response to thrombin after endothelial injury and/or thrombus formation will enhance inflammation in vasculature.
PAR 的表达在动脉粥样硬化斑块中富含平滑肌细胞的区域升高，在这些区域中，细胞向促炎或合成表型转变。在这项研究中，我们研究了凝血酶是否会促进血管平滑肌细胞（VSMC）的促炎表型，其特征是细胞因子和趋化因子合成增加。凝血酶不仅提高了 IL-6、CXCL8 和 CCL11 基因的转录本，而且还增强了人主动脉平滑肌细胞（HAoSMC）中 IL-6 和 CXCL8 蛋白的释放。凝血酶激活了 HAoSMC 中的 Akt、PKC 和 MAPK，LY294002、AKT IV、RO318220 和 GF109203X 以及二苯并碘在信使 RNA 和蛋白水平上显著抑制了凝血酶介导的 IL-6 和 CXCL8 的表达。SB202129 和 U0126 也显著减弱了凝血酶介导的 HAoSMC 中 IL-6 和 CXCL8 蛋白的释放。这些结果表明，凝血酶促进了人 VSMC 的促炎表型，而 PI3K、Akt、PKC、NADPH 氧化酶和 MAPK 参与了这一过程。我们提出，内皮损伤和/或血栓形成后凝血酶激活 VSMC 将增强血管中的炎症。
