Vol. 276, Issue 5, E856-E862, May 1999
Platelet-stimulated thrombin and PDGF are normalized by
insulin and Ca2+ channel blockers
Nighat N.
Kahn
Department of Medicine, Mount Sinai School of Medicine, New York
10029; and Spinal Cord Damage Research Center, Veterans Affairs Medical
Center, Bronx, New York 10468
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.
receptor; prostacyclin; prostaglandin
E1; coronary artery disease; platelet-derived growth factor adenosine
3',5',-cyclic monophosphate
