Background: Estriol, one of the estrogens inhibits platelet aggregation through nitric oxide synthase (NOS) activation. Furthermore, estriol could not inhibit platelet aggregation and synthesize NO in PRP from the subjects with acute myocardial infarction (AMI). Investigation was carried out to determine the mechanism of non-genomic expression of NO synthesis in platelet and to find the reason of the failure of the estrogen to inhibit platelet aggregation and to stimulate NO synthesis in AMI platelets.
Methods: Dermcidin isoform-2 (DMC-2) was prepared by electrophoresis. NO was determined by methemoglobin methods. The platelet membrane NOS was isolated by gel-electrophoresis. The binding characteristics of estriol to platelets were determined by enzyme linked immunosorbent assay.
Results: The increased synthesis of NO by 8 fold through allosteric activation was inhibited by tamoxifen, an estrogen receptor antagonist. The treatment of AMI platelets with 0.6nM estriol failed to increase both NO synthesis and to inhibit platelet aggregation by 2.0µM ADP due to down-regulation of estriol binding by 1.6fold to its own receptor for the preexisting biding of DMC-2.
Conclusion: The failure of estriol to inhibit platelet aggregation via NO synthesis was due to “cross-talk” between DMC-2 and estriol in the platelet surface in AMI.