ReferenceID 4938

Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells

Vascul Pharmacol

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

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Reference Id
4938
Evidence Id
21528
Core Evidence Id
21528
Source Reference Id
3135
Herb2 Reference Id
HBREF003932
Subject Paper Key
HBIN021260_33232770
Pubmed Id
33232770
Doi
10.1016/j.vph.2020.106822
Paper Title
Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells
Paper 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. METHODS: HUVEC were pre-incubated with colchicine 10 muM for 1 h and then stimulated with oxLDL (50 mug/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-kappaB/IkappaB axis was examined by western blot analysis and translocation assay. Finally, LOX-1 expression was also investigated. 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-kappaB/IkappaB pathway and LOX-1 expression. 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.
Journal
Vascul Pharmacol
Publish Year
2021
Experiment Subject
human; oxldl stimulated human vascular endothelial cells
Experiment Type
Cell Experiment
Phenotype Related
Cardiovascular Disease; Coronary Thrombosis; Atherosclerosclerosis
Paper Title Cn
Paper Title En
Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells
Bilingual Status
semi_complete