Platelet activity and phosphoinositide turnover increase with advancing age

: 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.: 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 [beta]-thrombeglobulin ([beta]-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.: There was a positive correlation with age for both adenosine diphosphate (ADP)-induced aggregation (1.25 [mu]M, R = 0.464, p 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[deg]C. A positive correlation was found between age and basal 32P-PIP2 (r = 0.640, p 32P-PIP (r = 0.676, p 32Pi incorporation into PIP2 correlated positively with in vitro aggregation (1.25 [mu]M ADP, R = 0.795, p 32Pi incorporation into PIP (1.25 [mu]M ADP, R = 0.815, p 32P-PIP2 (r = 0.768, p 32P-PIP (r = 0.505, p 32P-PIP2 hydrolysis (r = 0.694, p : Advancing age is associated with an increase in in vitro platelet aggregation, elevated [beta]-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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28905/1/0000742.pd