The clinical significance of platelet microparticle-associated microRNAs

Abstract

Abstract:Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~ 9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.

Milk MicroRNAs in Health and Disease

“…In humans, the idea of microRNA transfer between individuals was first validated when blood was found to contain numerous microRNAs that can be transmitted during transfusions (Provost, 2017) and that these microRNAs can impact immune system function (Laffont et al, 2013). Later on, transfer of microRNAs from the mother to the fetus through the placenta was described (Sadovsky, Mouillet, Ouyang, Bayer, & Coyne, 2015).…”

The role of microvesicles containing microRNAs in vascular endothelial dysfunction

“…Firstly, only selected part of the intracellular miRNAs are effectively transferred to recipient cells . miRNAs must be actively secreted from cells and selectively packaged into appropriate carriers, such as EVs (exosomes, MVs and apoptosis bodies), lipoproteins (LDL, HDL) and other ribonucleoprotein complexes . Selective and precise transport of miRNAs by MVs is the key step of extracellular miRNA‐mediated intercellular communication .…”

“…[61][62][63] miRNAs must be actively secreted from cells and selectively packaged into appropriate carriers, such as EVs (exosomes, MVs and apoptosis bodies), lipoproteins (LDL, HDL) and other ribonucleoprotein complexes. 64,65 Selective and precise…”

Not all good things come in big packages

“…Takahashi et al [14] review the principle and involvement of exosomal miRNAs in cancer. Focusing on the intracellular fraction of blood miRNAs, Provost [15] covers the clinical significance of platelets miRNAs. Desgagné et al [16] review the particularities and functions of lipoprotein-associated miRNAs.…”