Impaired platelet prostacyclin receptor activity: a monozygotic twin studydiscordant for spinal cord injury

Coronary artery disease (CAD) has been reported to occur prematurely in ind ividuals with spinal cord injury (SCI). Although persons with SCI have meta bolic abnormalities that may predispose them to CAD, other potential aetiol ogies may also be operative. Increased platelet aggregation, among other fa ctors, initiates thrombus formation at the site of the vessel injury, which may acutely obstruct arterial blood flow. Prostacyclin is known to have a beneficial effect to inhibit platelet aggregation and prevent thrombus form ation. Platelets were studied from 12 pairs of monozygotic twins, one co-tw in with SCI. Each twin pair had similar patterns of platelet aggregation wi th adenosine diphosphate (ADP), thrombin or collagen, as well as inhibition of platelet aggregation by prostacyclin (PGE(1)/I-2) and synthesis of cycl ic adenosine mono phosphate (AMP) by the prostanoid. However, the twin pair s differed in their response to PGE(1)/I-2 inhibition of platelet-stimulate d thrombin generation that was completely inhibited in non-SCI platelets bu t not in SCI platelets. Scatchard analysis of the binding of H-3-prostaglan din E-1, a stable prostacyclin receptor probe, showed the presence of one h igh-affinity (K-d1 = 8.1 +/- 2.8 nM; n(l) = 168 +/- 35 sites per platelet) and one low-affinity (K-d2 = 1.1 +/- 0.22 muM; n(2) = 1772 +/- 220 sites pe r cell) prostacyclin receptor in normal platelets, whereas in SCI platelets there was a significant loss (P <0.00l) of high-affinity receptor sites (K -d1 = 6.34 +/- 1.80 nM; n(1) = 42 +/- 11 sites per platelet) with no signif icant change in the low-affinity receptor sites (K-d2 = 1.2 +/- 0.23 muM; n (2) = 1860 +/- 412 sites per cell). These discordant platelet findings in i dentical twin pairs raises the possibility of an environmental aetiology fo r accelerated CAD in those with SCI. The loss of inhibitory effect of PGI(2 ) on thrombin generation in the twin with SCI appears to be because of loss of platelet high-affinity prostanoid receptors, which may contribute to at herogenesis in individuals with SCI.