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

Abstract

• Unique dataset of human platelet mRNA, miRNA, and physiology reveals mRNAs and miRNAs that differ by age and gender.• Interactive public web tool (www.plateletomics.com) provides biologic insights into platelet function and gene expression.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. (Blood. 2014;123(16):e37-e45)

RASA3 is a critical inhibitor of RAP1-dependent platelet activation

“…In previous work, Smolenski and colleagues suggested a role for RAP1GAP2 in platelet activation (29). However, RNA and protein expression profiling demonstrated that RAP1GAP2 is very weakly expressed in human platelets and virtually absent in mouse platelets (30)(31)(32). The same studies identified the dual specificity GAP, RASA3, as the most abundant RAP-GAP expressed in platelets, with protein expression levels comparable to that of CalDAG-GEFI.…”

Nouvelle Cuisine: Platelets Served with Inflammation

“…These molecules in platelets may come from different sources, such as those inherited from megakaryocytes, those absorbed from the plasma, or those generated de novo. With regard to de novo synthesis of molecules in platelets, although platelets are anucleate, they express significant amounts of RNA, including mRNAs (e.g., premature and mature RNA), structural and catalytic RNAs (e.g., ribosomal and tRNA), regulatory RNAs (e.g., microRNA), and noncoding RNA (e.g., anti-sense RNA) (90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105). More recently, it also was revealed that platelets contain all of the molecular machinery to translate mRNA into proteins, and they have the ability to transfer RNA to recipient cells where it can regulate cellular function (101-104).…”

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

“…Platelets do not contain a nucleus and therefore, regulatory effects of coding and non-coding RNA remain controversial. mRNA analysis and transcriptomics as well as non-coding RNA are rapidly evolving fields of research, which provide crucial insights regarding age, gender and demographic variants that determine differences in platelet hyper-hyporeactivity (61,62). Recent evidence suggest that miRNA containing microparticles derived from platelets are involved in regulation of gene expression in endothelial cells by means of functional Argonaute 2 (Ago2) miRNA complexes (63).…”

“…Data of this extensive cohort reveal differential expression of 129 mRNAs and 15 miRNAs by age, 54 mRNAs and 9 miRNAs by gender highlighting the inverse relationship between these mRNAs and miRNAs. An interactive web tool has been generated (www.plateletomics.com) which permits queries regarding RNA levels and associations among RNA, platelet aggregation and demographic variables (61). Platelet miRNAs bind to important target mRNAs that govern P2Y12, GPIIb/IIIa, and cyclic AMP-dependent protein kinase A.…”