Effects of colchicine on tissue factor in oxLDL-activated T-lymphocytes

J Thromb Thrombolysis. 2022 Apr;53(3):739-749. doi: 10.1007/s11239-021-02585-2. Epub 2021 Oct 20.

Abstract

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.

Keywords: Colchicine; Rosuvastatin; T-lymphocyte; Thrombosis; Tissue factor.

MeSH terms

  • Acute Coronary Syndrome* / drug therapy
  • Colchicine / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Lipoproteins, LDL
  • NF-kappa B / metabolism
  • Rosuvastatin Calcium / pharmacology
  • T-Lymphocytes / metabolism
  • Thromboplastin / genetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • NF-kappa B
  • oxidized low density lipoprotein
  • Rosuvastatin Calcium
  • Thromboplastin
  • Colchicine