Molecular analysis of heterogeneity in human platelet aggregation response

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There is a significant inter-individual divergence in the platelet aggregation response to arginine vasopressin (AVP). In the present study, high-throughput microarray analysis was conducted to explore molecules, which are responsible for the heterogeneity. Responders and non-responders were divided using platelet aggregation analyzer MCM hematracer 313 (Model PAM-12C). Hitachi Ace-Gene micro array analysis showed characteristic gene expression profiling. Namely, responder platelets had increased gene expressions of sodium channel, voltage-gated, type., alpha, mannose-P-dolichol utilization defect 1、eukaryotic translation termination factor 1、cysteine and glycine-rich protein 2、and general transcription factor IIH, polypeptide 2,44kDa. In non-responder platelets, genes including component of oligomeric golgi complex 6、Hermansky-Pudlak syndrome 3、PERM domain containing 1、adenosine monophosphate deaminase 2 (isoform L) nudix-type motif 1、and cell growth regulator with ring finger domain 1 were upregulated. Mass spectrometry analysis demonstrated increased platelet protein levels of protease serine 4 isoform B、and keratin 1b、trypsin family in responders and of TPMsk1、TPM3 protein、and YWHAZ protein in non-responders. There were also increased microRNA levels including hsa let 7d、hsa let 7e、hsa miR 198、hsa miR 99b、and hsa miR 98 in AVP stimulated peripheral CD34(+) stem cells (megakaryocyte progenitor cells). AVP Vla receptor gene polymorphism 242C/T showed an association with its gene expression. From these results, numbers of factors were likely to be responsible for the inter-individual heterogeneity in the platelet aggregation response to AVP.