PLATELET CALCIUM HOMEOSTASIS IS ABNORMAL IN PATIENTS WITH SEVERE ARTERIOSCLEROSIS

To evaluate platelet calcium homeostasis in a typical thrombosis-prone clinical condition, 14 patients with severe arteriosclerosis and 11 h ealthy control subjects were studied. Platelet intracellular free calc ium concentration ([Ca2+](i)) was evaluated by means of the fluorescen t probe fura 2 under resting conditions and after challenge with 0.05, 0.1, and 0.5 U/mL thrombin (final concentrations). Three different co ncentrations of extracellular ionized calcium ([Ca2+](e)) were used: 1 mmol/L, 1 mu mol/L, and <1 nmol/L. Resting platelet [Ca2+](i) was sig nificantly higher (P<.001) in patients than in control subjects. After addition of 0.05 U/mL thrombin, the relative increase of [Ca2+](i) wa s lower in patients than in control subjects in each of the three [Ca2 +](e) conditions (P=.05 at 1 mmol/L, P=.02 at 1 mu mol/L, and P=.04 at <1 nmol/L). After addition of 0.1 U/mL thrombin, the relative increas e of [Ca2+](i) was lower in patients than in control subjects under tw o [Ca2+](e) conditions, 1 mu mol/L and <1 nmol/L (P=.04 and P=.03, res pectively). With 0.5 U/mL thrombin, a trend toward lower values in pat ients than in control subjects was observed, reaching statistical sign ificance (P=.03) only at <1 nmol/L [Ca2+](e). These results suggest th at calcium homeostasis is abnormal in platelets from patients with sev ere arteriosclerosis and probably reflects a chronic activation.