Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via Sergio Pansini 5, 80131, Naples, Italy.
Department of Translational Medical Sciences, Section of Cardiology, University of Campania "Luigi Vanvitelli", Naples, Italy.
J Thromb Thrombolysis. 2022 Apr;53(3):739-749. doi: 10.1007/s11239-021-02585-2. Epub 2021 Oct 20.
Several studies have shown that T-cells might be involved in pathophysiology of acute coronary syndromes (ACS). Tissue factor (TF) plays a key role in ACS. Many evidences have indicated that some statins reduce TF expression in several cell types. However, literature about rosuvastatin and TF and about statins effects on T-cells is still scanty. Colchicine is an anti-inflammatory drug recently proven to have beneficial effects in ACS via unknown mechanisms. This study investigates the effects of colchicine and rosuvastatin on TF expression in oxLDL-activated T-cells. T-cells, isolated from buffy coats of healthy volunteers, were stimulated with oxLDL (50 µg/dL). T-cells were pre-incubated with colchicine (10 µM) or rosuvastatin (5 µM) for 1 h and then stimulated with oxLDL (50 μg/mL). TF gene (RT-PCR), protein (western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. NF-κB/IκB axis was examined by western blot analysis and translocation assay. Colchicine and rosuvastatin significantly reduced TF gene, and protein expression and procoagulant activity in oxLDL stimulated T-cells. This effect was associated with a significant reduction in TF surface expression as well as its procoagulant activity. These phenomena appear modulated by drug effects on the transcription factor NF-kB. Rosuvastatin and colchicine prevent TF expression in oxLDL-stimulated T-cells by modulating the NF-κB/IκB axis. Thus, we speculate that this might be another mechanism by which these drugs exert benefic cardiovascular effects.
几项研究表明，T 细胞可能参与急性冠状动脉综合征 (ACS) 的病理生理学。组织因子 (TF) 在 ACS 中起关键作用。许多证据表明，一些他汀类药物可降低几种细胞类型中的 TF 表达。然而，关于瑞舒伐他汀和 TF 以及他汀类药物对 T 细胞影响的文献仍然很少。秋水仙碱是一种抗炎药物，最近通过未知机制被证明对 ACS 有益。本研究探讨了秋水仙碱和瑞舒伐他汀对 oxLDL 激活的 T 细胞中 TF 表达的影响。从健康志愿者的白细胞中分离出 T 细胞，用 oxLDL（50µg/dL）刺激。T 细胞用秋水仙碱（10µM）或瑞舒伐他汀（5µM）预孵育 1 小时，然后用 oxLDL（50μg/mL）刺激。测量 TF 基因（RT-PCR）、蛋白（western blot）、表面表达（FACS）和促凝血活性（FXa 生成测定）。通过 western blot 分析和转位测定研究 NF-κB/IκB 轴。秋水仙碱和瑞舒伐他汀可显著降低 oxLDL 刺激的 T 细胞中 TF 基因、蛋白表达和促凝血活性。这种作用与 TF 表面表达及其促凝血活性的显著降低有关。这些现象似乎通过药物对转录因子 NF-kB 的作用来调节。瑞舒伐他汀和秋水仙碱通过调节 NF-κB/IκB 轴来阻止 oxLDL 刺激的 T 细胞中 TF 的表达。因此，我们推测这可能是这些药物发挥有益心血管作用的另一种机制。
