Impaired prostacyclin receptors in platelets from spinal cord injured subjects: A twin study

Premature coronary artery disease (CAD) is the leading cause of death in individuals with spinal cord injury (SCI). Platelets were studied from 12 pairs of monozygotic twins (confirmed by DNA analyses), one twin in each pair had SCI. Platelet aggregation with ADP, thrombin or collagen was similar in the SCI and nonSCI twin groups. Inhibition of platelet aggregation by prostacyclin (PGI2) and prostanoid-induced cyclic AMP synthesis was comparable in the two groups. However, PGI2 completely inhibited the platelet-stimulated thrombin generation in normals, failed to do so in those with SCI. Comparing SCI with nonSCI twins. Scatchard analysis of the binding of 3H-prostaglandin E, showed a significant loss of high-affinity receptor number (n,=40±12 vs. n,= 170±28 sites/platelet, p>0.001) with no significant change in receptor affinity (kd.=5.9+2.35 vs. kd,=7.9±2.9 nM); platelet low-affinity receptor number (n:=1770±230 vs. n2 = 1798±443 sites/cell) and receptor affinity kd2=1.02±0.3 vs. kd2=1.1±0.33 uM) were not significantly different. The occurrence of these platelet abnormalities in identical twins suggests non-genetic causes for CAD in SCI. These results indicate that the loss of inhibitory effect of PGI2 on thrombin generation in the SCI twin was due to the loss of platelet high-affinity prostanoid receptors, which may contribute to atherogenesis in individuals with SCI.