Changes in signal transduction in the platelets of patients with peripheral occlusive arterial disease

Background. The finding that platelets of patients with peripheral occlusiv e arterial disease (POAD) circulate in an activated state prompted us to st udy platelet signal transduction. We hypothesised that platelet hyperreacti vity is caused by changes in intracellular signalling. Methods. Experimental design: a single blood sample was taken from the ante cubital vein of each participant prior to the start of intravenous treatmen t with prostaglandins. Setting: patients were recruited from our inpatient Department of Cardiology and Angiology at the University Hospital. Particip ants: 15 hospitalised patients with symptomatic POAD were randomly selected . Patients receiving antiplatelet drugs and those with diabetes were exclud ed. The control group consisted of 15 healthy volunteers from the medical s taff. Interventions: blood tests were performed on the day of admission bef ore any therapeutic intervention. Measures: the platelet activation marker P-selectin was quantified on peripheral blood platelets before and after in vitro stimulation with platelet agonists (adenosine diphosphate, thrombin receptor activator peptide-6). The signal transduction cascade was also sel ectively blocked by preincubation with either: 1) forskolin, 2) phospholipa se C inhibitor U-73122, or 3) bisindolylmaleimide. Results. A stronger inhibitory effect on ADP-stimulated platelets was seen in patients with U-73122, as indicated by a decrease in mean fluorescence i ntensity of 51% versus 34% in controls (p<0.0005). Conclusions. Our findings support the assumption that changes in platelet s ignal transduction in POAD lead to platelet hyper-reactivity.