Microparticles as intercellular carriers of the microRNA signal: insights for novel diagnostic and therapeutic approaches.

2016; 115: 311-323. Microparticles (MPs) represent extracellular vesicles that are released from their parental cell by budding of the plasma membrane and are known to harbour an opulent spectrum of bioactive substances including microRNA (miRNA). As a multitude of induction pathways together with inclusive and exclusive sorting mechanisms are operative during the generation of MPs, the molecular composition of MPs reflects the type and condition of cellular activation. Circulating MPs may transfer their components and content to trigger distinct effects on selectively responsive target cells not only in their local environment but also throughout the circulatory system, resulting in cellular activation, phenotypic modification, and reprogramming of cell function (1). Such a transcellular shuttle system establishes a versatile communication network in which biological signals and properties among cells can be selectively exchanged. The identification of MPs as carriers of miRNAs, which control a variety of biological pathways by providing posttranscriptional regulation of gene expression, highlights the relevance of MPs in health and disease (2). As carriers, MPs protect extracellular miRNA from plasma ribonucleases and facilitate dissemination of the miRNA signal to sites distant from their origin. In this issue of Thrombosis and Haemostasis, Laffont et al. (3) now demonstrate that platelet MPs can deliver functional miRNA-126-3p, modify the transcriptome and secretome of macrophages and stimulate their phagocytic activity. MP interaction with macrophages is of particular interest, as macrophages dominantly operate the clearance of MPs in vivo. Platelet MPs are internalised by macrophages within few hours and transfer of miRNA-126-3p results in downregulated expression of predicted mRNA targets. Although the underlying mechanism remains unclear, exposure of macrophages to platelet MPs results in substantial modification of their genetic machinery with consecutive differential expression of 66 miRNAs and 653 RNAs as well as reprogramming of macrophages towards a phagocytic phenotype. Beyond findings that delivery of miR-126-3p by endothelial MPs promotes endothelial regeneration through recruiting angiogenic cells (4), this novel mechanism may provide a complementary explanation for atheroprotective effects of miR-126 from a different cellular source in a distinct cell type (3). Despite significant progress in the field of MP research, the determinants and regulatory factors of miRNA sorting and packaging into MPs, targets and functions of transferred miRNA, and involved molecular mechanisms of action and their conditions in various target cell types are still poorly understood. Elucidation of such processes and particularly decryption of the unique signature of miRNA in carriers such as MPs and exosomes provide an intriguing opportunity for the development of diagnostic biomarkers. Additionally, customisation of vesicles with a distinct set of miRNAs and therefore a concerted manipulation of the miRNA signal may advance our current therapeutic strategies.