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 (PGI(2)) may retard atherogenesis through its inhibit ory effects on platelet function, the role of PGI(2) on SCI platelets was d etermined. The SCI platelets were neither hypersensitive to aggregating ago nists nor resistant to the inhibitory effect of PGI(2), but PGI(2) failed t o inhibit platelet-stimulated thrombin generation and the release of platel et-derived growth factor (PDGF) in SCI. Because thrombin and PDGF are ather ogenic mitogens, the generation of these mitogens was investigated. Both th e release of PDGF and thrombin generation in SCT platelets were higher when compared with control (n = 12). Treatment of non-SCI platelets with 100 nM PGE(1) (a stable probe of PGI(2)) inhibited the release of the mitogens by 90% (P < 0.001), with no effect on SCI platelets. Scatchard analysis of pr ostaglandin E-1 (PGE(1)) binding showed a 70% decrease of PGI(2) receptors on the SCI platelet surface. Treatment of SCI platelets with insulin or Ca2 + channel blockers restored the PGI(2)-receptor number and "normalized" the inhibition of PDGF release and thrombin generation by PGI(2).