Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Helmholtzstr 20, 89081 Ulm, Germany.
J Thromb Thrombolysis. 2010 Aug;30(2):164-71. doi: 10.1007/s11239-010-0447-7.
Human cytomegalovirus (HCMV) establishes a life-long persistent infection. HCMV infection could be associated with chronic inflammatory diseases, such as cardiovascular disease and atherosclerosis. Here we observed that in HCMV (AD-169) pre-exposed human umbilical vein endothelial cells (HUVEC), thrombin-induced expression of IL-1alpha and M-CSF is markedly enhanced compared to the un-exposed cells. Study of the expression of thrombin receptor genes in HUVEC showed that HCMV triggered a time- and concentration-dependent expression of the thrombin receptors PAR1, PAR3 and PAR4 at the mRNA level. Induction of PAR1 and PAR3 mRNA expression is due to transcriptional activation of their promoters as shown by gene reporter assay. Furthermore, the virus induced expression of PAR1 and PAR3 but not PAR4 proteins, as analyzed by Western immunoblotting. However, flow cytometric analysis revealed that only PAR3, expressed at very low level in control HUVEC, is induced at the surface during the exposure to the virus. Our data suggest that although exposure to HCMV induces a minor increase of cell-surface receptors expression, it does make endothelial cells more responsive to additional thrombin stimulation.
人巨细胞病毒（HCMV）建立了终身持续感染。HCMV 感染可能与慢性炎症性疾病有关，如心血管疾病和动脉粥样硬化。在这里，我们观察到在 HCMV（AD-169）预先暴露的人脐静脉内皮细胞（HUVEC）中，与未暴露的细胞相比，凝血酶诱导的 IL-1alpha 和 M-CSF 的表达显著增强。对 HUVEC 中凝血酶受体基因表达的研究表明，HCMV 在 mRNA 水平上触发了凝血酶受体 PAR1、PAR3 和 PAR4 的时间和浓度依赖性表达。基因报告实验表明，PAR1 和 PAR3 mRNA 表达的诱导是由于其启动子的转录激活。此外，病毒诱导 PAR1 和 PAR3 蛋白的表达，但不诱导 PAR4 蛋白的表达，如 Western 免疫印迹分析所示。然而，流式细胞术分析显示，仅在对照 HUVEC 中低表达的 PAR3，在暴露于病毒时在表面被诱导。我们的数据表明，尽管 HCMV 的暴露会轻微增加细胞表面受体的表达，但它确实使内皮细胞对额外的凝血酶刺激更敏感。
