Author + information
- Giovanni Cimminoa,b,
- Stefano Contea,b,
- Andrea Morelloa,b,
- Grazia Pellegrinoa,b,
- Giovanni Ciccarellia,b,
- Michele De Paulisa,b,
- Plinio Cirilloa,b and
- Paolo Golinoa,b
Background: Tissue factor (TF) exposure is the key trigger of thrombus formation. Oxidized low-density lipoproteins (oxLDL) induce TF in endothelial cells (ECs), suggesting that oxLDL may act locally promoting thrombosis in atherosclerotic lesions. Colchicine (COL) is an anti-inflammatory agent that influences cytoskeleton dynamics with proven cardiovascular protective effects. However, the molecular mechanism by which COL exerts these properties is unknown. We aim at investigating if COL affects TF expression in oxLDL treated ECs by interfering with microtubule dynamic.
Methods: ECs were pretreated with COL 50µM and then exposed to oxLDL 50µg/mL. TF-mRNA levels were evaluated at 2 hrs by real-time PCR. TF protein expression and activity was measured by western blot/FACS analysis and activity assay, respectively. LIMK-1 and Cofilin protein levels, two kinases involved in cytoskeleton dynamics were also evaluated.
Results: COL significantly reduced TF expression in oxLDL treated ECs at both gene (Fig. A) and protein levels (Fig. B). A significant decrease in TF surface expression, as well as its procoagulant activity was also observed. COL also affected LIMK-1 and Cofilin by reducing expression of both non-phosphorylated forms and increasing expression of pospho-LIMK1.
Conclusions: Our study suggests that the cardiovascular protective effects of COL may be related, at least in part, to its inhibitory effects on TF expression on ECs by interfering with cytoskeleton dynamic.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: MicroRNAs and Beyond in Vascular Medicine
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1127-351
- 2017 American College of Cardiology Foundation