Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics.

There is little data considering relationships among human RNA, demographic variables, and primary human cell physiology. The platelet RNA and expression-1 study measured platelet aggregation to arachidonic acid, ADP, protease-activated receptor (PAR) 1 activation peptide (PAR1-AP), and PAR4-AP, as well as mRNA and microRNA (miRNA) levels in platelets from 84 white and 70 black healthy subjects. A total of 5911 uniquely mapped mRNAs and 181 miRNAs were commonly expressed and validated in a separate cohort. One hundred twenty-nine mRNAs and 15 miRNAs were differentially expressed (DE) by age, and targets of these miRNAs were over-represented among these mRNAs. Fifty-four mRNAs and 9 miRNAs were DE by gender. Networks of miRNAs targeting mRNAs, both DE by age and gender, were identified. The inverse relationship in these RNA pairs suggests miRNAs regulate mRNA levels on aging and between genders. A simple, interactive public web tool (www.plateletomics.com) was developed that permits queries of RNA levels and associations among RNA, platelet aggregation and demographic variables. Access to these data will facilitate discovery of mechanisms of miRNA regulation of gene expression. These results provide new insights into aging and gender, and future platelet RNA association studies must account for age and gender.

Clot Retraction and Its Correlation with the Function of Platelet Integrin αIIbß3.

Clot retraction results from retractions of platelet filopodia and fibrin fibers and requires the functional platelet αIIbß3 integrin. This assay is widely used to test the functions of platelets and fibrinogen as well as the efficacy of fibrinolysis. Changes in clot retraction have been found in a variety of hemostatic abnormalities and, more recently, in arterial thrombosis. Despite its broad clinical use and low cost, many aspects of clot retraction are poorly understood. In the present study, we performed two clinical standard clot retraction assays using whole-blood and platelet-rich plasma (PRP) samples to determine how clot retraction correlates with platelet counts and mean volume, the density of αIIbß3 integrin and PLA genotypes, and plasma fibrinogen levels. We found that clot retraction was affected by platelet counts, but not mean platelet volume. It correlated with the surface density of the integrin αIibß3, but not PLA genotypes. These results indicate that clot retraction measures a unique aspect of platelet function and can serve as an additional means to detect functional changes in platelets.