PLATELET ACTIVITY AND PHOSPHOINOSITIDE TURNOVER INCREASE WITH ADVANCING AGE

purpose: Blood platelet activity increases with advancing age. This study was designed to determine if changes in a key signal-transducing mechanism in the platelet, phosphoinositide turnover, are associated with the enhanced platelet activity seen in aging. patients and methods: Platelets were harvested from a total of 40 healthy, non-obese, 22- to 62-year-old individuals, free of any clinical evidence of atherosclerotic vascular disease, and having normal serum laboratory lipid levels. Studies of platelet activity included measurement of in vitro platelet aggregation and plasma β-thrombeglobulin (β-TBG), a marker of in vivo platelet secretion. Basal and thrombin-stimulated phosphoinositide turnover was measured following [32P]-orthophosphate incorporation into the various phospholipids, isolation of the phosphoinositides and phosphatidic acid by thin-layer chromatography and autoradiography, and quantification by liquid scintillation spectroscopy of these radiolabeled phospholipids. results: There was a positive correlation with age for both adenosine diphosphate (ADP)-induced aggregation (1.25 μM, r = 0.464, p <0.001; 2.5 μM, r = 0.386, p <0.05) and plasma β-TBG (r = 0.381, p <0.055). There was a time-dependent increase of [32P]orthophosphate (32Pi) incorporation into platelet phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-phosphate (PIP), and isotopic equilibrium was reached by 120 minutes at 37°C. A positive correlation was found between age and basal 32P-PIP2 (r = 0.640, p <0.001) and 32P-PIP (r = 0.676, p <0.0005). Basal 32Pi incorporation into PIP2 correlated positively with in vitro aggregation (1.25 μM ADP, r = 0.795, p <0.0001; 2.5 μM ADP, r = 0.755, p <0.0005) as did 32Pi incorporation into PIP (1.25 μM ADP, r = 0.815, p <0.0001; 2.5 μM ADP, r = 0.795, p <0.0001). There was also a positive correlation between plasma β-TBG levels and basal 32P-PIP2 (r = 0.768, p <0.005) and 32P-PIP (r = 0.505, p <0.066). Finally, increasing age correlated with thrombin (4 U/mL)-stimulated 32P-PIP2 hydrolysis (r = 0.694, p <0.01) and phosphatidic acid formation (r = 0.556, p <0.05). conclusion: Advancing age is associated with an increase in in vitro platelet aggregation, elevated β-TBG levels, and enhanced phosphoinositide turnover. Because phosphoinositide turnover is associated with stimulus-coupled platelet activation, the increased basal and stimulated phosphoinositide turnover may mediate the increase in platelet activity with aging. © 1990.