Abstract 10538: Endogenous Prostacyclin Inhibitor Coupling Factor 6 Enhances Spontaneous Platelet Micro-Aggregation in Patients with Recent Onset Stroke Independently of Anti-Platelet Therapy
Backgrounds: Spontaneous platelet micro-aggregation is a marker for the prognosis of patients with cardiovascular diseases. Coupling factor 6 (CF6) is a pro-atherogenic molecule, and functions after binding to ecto-F1Fo complex of ATP synthase. Platelet has ecto-F1Fo complex at the surface, and its spontaneous micro-aggregation may be enhanced by CF6.
Methods: We investigated the effect of CF6 on platelet aggregation in the platelet-rich plasma obtained from 339 patients with recent onset ischemic stroke (atherothrombotic, 173; lacunar, 71; embolism 95) and 43 adult healthy controls. Light intensities of small (9-25μ n), medium (25-50μ m), and large (50-70μ m) platelet aggregates were measured by the laser light scattering aggregometer (PA-200C) with or without adenosine diphosphate (ADP, 2μ M) or collagen (1μ g/ml). Cytosolic free calcium concentration was measured by fura-2/AM fluorescence technique.
Results: In spontaneous platelet aggregation, area under curve (AUC) of small-sized aggregates (mV*count*min) was greater in stroke patients (atherothrombotic 1.39±0.13×107, lacunar 1.17±0.14×107, embolism 1.35±0.16×107) than in healthy controls (0.80±0.12×107, all p<0.01). Administration of 10-7M CF6 increased AUC of small-sized aggregates by 38.9±6.4% (p<0.01) irrespectively of the treatment with aspirin, clopidogrel, ticlopidine, or cirostazole. Pretreatment with indomethacin in vitro attenuated spontaneous platelet aggregation without affecting CF6-induced increase in small-sized aggregates. Pretreatment with antibodies against CF6 and α or β-subunit of ecto-F1 suppressed not only spontaneous small-sized aggregates but its increase by CF6. CF6 increased AUC of large-sized aggregates induced by ADP from 3.08±0.65×107 to 3.52±0.65×107 (p<0.01) while increasing the cytosolic calcium concentration.CF6 did not influence collagen-induced large-sized aggregates.
Conclusions: CF6 enhanced spontaneous micro-aggregation of platelets through ecto-F1Fo complex in patients with recent onset stroke independently of anti-platelet therapy. CF6 can be a novel target molecule in anti-platelet therapy against cardiovascular events in humans.
- © 2011 by American Heart Association, Inc.