Author + information
- Giovanni Cimminoa,b,
- Stefano Contea,b,
- Andrea Morelloa,b,
- Grazia Pellegrinoa,b,
- Alberto Morelloa,b,
- Saverio D'Eliaa,b,
- Gaetano Calìa,b,
- Bruno Trimarcoa,b,
- Paolo Golinoa,b and
- Plinio Cirilloa,b
Background: Platelet aggregation and thrombus formation are key events in thrombotic disorders. Once activated, platelets undergo extensive cytoskeleton rearrangement (CR). Colchicine (COL) is an anti-inflammatory agent proven to reduce major cardiovascular events in stable CAD patients. However, the molecular mechanisms by which COL exerts these protective effects are unknown. We aim at investigating if COL interferes with platelet aggregation and CR.
Methods: Platelets isolated from healthy volunteers were activated with ADP 20µM with/without COL 50µM pretreatment. After stimulus, aggregation was measured by light aggregometry at 30, 60 and 90 minutes. Expression of cofilin and LIM domain kinase 1(LIMK1), two kinases involved in CR, was evaluated at baseline, 15, 45, 120 and 180 seconds by western blot. Microtubules structure was analyzed by immunohistochemistry.
Results: COL pretreatment significantly blunted ADP-induced platelet aggregation (up to 40%). This effect was associated to a marginal band loss and cytoskeleton disarrangement (Fig. C) as compared to baseline (Fig. A) and ADP treated (Fig. B), indicating inhibition of cofilin and LIMK1 activity, resulting in microtubules depolymerization.
Conclusions: Our data indicate that COL exerts anti-platelet effects in vitro via inhibition of kinases involved in cytoskeleton rearrangement, suggesting that the beneficial cardiovascular properties of COL may be due, at least in part, to an inhibitory effect of platelet function.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Cutting Edge Vascular Medicine
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1205-357
- 2017 American College of Cardiology Foundation