Platelet-stimulated thrombin and PDGF are normalized by insulin and Ca2+ channel blockers.

Coronary artery disease is accelerated in chronic spinal cord injury (SCI). Because prostacyclin (PGI2) may retard atherogenesis through its inhibitory effects on platelet function, the role of PGI2 on SCI platelets was determined. The SCI platelets were neither hypersensitive to aggregating agonists nor resistant to the inhibitory effect of PGI2, but PGI2 failed to inhibit platelet-stimulated thrombin generation and the release of platelet-derived growth factor (PDGF) in SCI. Because thrombin and PDGF are atherogenic mitogens, the generation of these mitogens was investigated. Both the release of PDGF and thrombin generation in SCI platelets were higher when compared with control (n = 12). Treatment of non-SCI platelets with 100 nM PGE1 (a stable probe of PGI2) inhibited the release of the mitogens by 90% (P < 0.001), with no effect on SCI platelets. Scatchard analysis of prostaglandin E1 (PGE1) binding showed a 70% decrease of PGI2 receptors on the SCI platelet surface. Treatment of SCI platelets with insulin or Ca2+ channel blockers restored the PGI2-receptor number and "normalized" the inhibition of PDGF release and thrombin generation by PGI2.