Aging and platelet GPIIb-IIIa exposure

We determined whether changes in GPIIb-IIIa expression, a key step in platelet aggregation, or inhibition by the actin cytoskeleton or cAMP accounted for the increased sensitivity of platelets from older subjects to ADP aggregation. 13 healthy young (31 yrs) and 11 healthy elderly (72 yrs) subjects were studied. No aging difference was found in resting or ADP (5×10-5M) stimulated GPIIb-IIIa complex expression. 60% of expressed GPIIIa was used to form GPIIb-IIIa complexes. Inhibition of actin polymerization by cytochalasin D enhanced ADP induced GPIIb-IIIa exposure similarly in young and old subjects. Expression of activated GPIIb-IIIa but not GPIIIa or total GPIIb-IIIa complexes was inhibited to a greater extent by db-cAMP in older subjects (80±2 vs 60±5%, P=0.02). The age-associated increase in platelet aggregability is not due to altered GPIIb-IIIa complex expression. Increased affinity of the GPIIb-IIIa receptor for fibrinogen or increased response to fibrinogen binding may account for the age-associated increased reactivity of platelets.