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

Authors :
Giusi Barra
Giovanni Cimmino
Paolo Golino
Raffaele De Palma
Plinio Cirillo
Stefano Conte
Grazia Pellegrino
Akhmetzhan Sugraliyev
Cirillo, Plinio
Conte, Stefano
Pellegrino, Grazia
Barra, Giusi
De Palma, Raffaele
Sugraliyev, Akhmetzhan
Golino, Paolo
Cimmino, Giovanni
Cirillo, P.
Conte, S.
Pellegrino, G.
Barra, G.
De Palma, R.
Sugraliyev, A.
Golino, P.
Cimmino, G.
Publication Year :
2021

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 (50µg/dL). T-cells were pre-incubated with colchicine (10µM) or rosuvastatin (5µM) for 1h and then stimulated with oxLDL (50μg/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.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....4e30c8459e06f240ddd1689d25055d04