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Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells.

Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells.

Authors :
Cimmino G
Conte S
Morello A
Pellegrino G
Marra L
Calì G
Golino P
Cirillo P
Source :
Vascular pharmacology [Vascul Pharmacol] 2021 Apr; Vol. 137, pp. 106822. Date of Electronic Publication: 2020 Nov 21.
Publication Year :
2021

Abstract

Background: Tissue Factor (TF) plays a pivotal role in coronary thrombosis. Oxidized low-density lipoproteins (oxLDL) are crucial in development of atherosclerosclerosis. Moreover, oxLDL are known to induce TF expression on several cell types including endothelial cells. The lectin-type oxidized LDL receptor 1 (LOX-1) represent the oxLDL receptor. Colchicine is an anti-mitotic drug recently proven to have beneficial effects in cardiovascular disease via unknown mechanisms. Thus, we aim at investigating colchicine effects on TF expression in oxLDL stimulated human vascular endothelial cells (HUVEC). Some molecular mechanism(s) potentially involved were investigated.<br />Methods: HUVEC were pre-incubated with colchicine 10 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. TF translocation to cell surface was investigated by immunofluorescence. NF-κB/IκB axis was examined by western blot analysis and translocation assay. Finally, LOX-1 expression was also investigated.<br />Results: Colchicine significantly reduced TF gene and protein expression as well as its procoagulant activity in oxLDL-treated HUVEC. These effects seem to be related mainly to action of colchicine on microtubules that, in turn, modulate TF trafficking in the cytoplasm, NF-κB/IκB pathway and LOX-1 expression.<br />Conclusions: Data of the present study, although in vitro, indicate that one of the hypothetical mechanisms by which colchicine exert protective cardiovascular effects might be its ability to inhibit the pro-thrombotic activity of oxLDL.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1879-3649
Volume :
137
Database :
MEDLINE
Journal :
Vascular pharmacology
Publication Type :
Academic Journal
Accession number :
33232770
Full Text :
https://doi.org/10.1016/j.vph.2020.106822