title: Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles.
abstract: Platelets play a crucial role in the maintenance of hemostasis, as well as in thrombosis. Upon activation, platelets release small membrane-bound microparticles (MPs) containing bioactive proteins and genetic materials from their parental cells that may be transferred to, and exert potent biological effects in, recipient cells of the circulatory system. Platelets have been shown to contain an abundant and diverse array of microRNAs, and platelet-derived MPs are the most abundant microvesicles in the circulation. Here we demonstrate that human platelets activated with thrombin preferentially release their miR-223 content in MPs. These MPs can be internalized by human umbilical vein endothelial cells (HUVEC), leading to the accumulation of platelet-derived miR-223. Platelet MPs contain functional Argonaute 2 (Ago2)•miR-223 complexes that are capable of regulating expression of a reporter gene in recipient HUVEC. Moreover, we demonstrate a role for platelet MP-derived miR-223 in the regulation of 2 endogenous endothelial genes, both at the messenger RNA and protein levels. Our results support a scenario by which platelet MPs may act as intercellular carriers of functional Ago2•microRNA complexes that may exert heterotypic regulation of gene expression in endothelial cells, and possibly other recipient cells of the circulatory system.
authors: Centre Hospitalier Universitaire de Québec Research Center/Centre Hospitalier de l'Université Laval, Quebec, Canada.
authors: Benoit
authors: B
authors: Laffont
authors: Aurélie
authors: A
authors: Corduan
authors: Hélène
authors: H
authors: Plé
authors: Anne-Claire
authors: AC
authors: Duchez
authors: Nathalie
authors: N
authors: Cloutier
authors: Eric
authors: E
authors: Boilard
authors: Patrick
authors: P
authors: Provost
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D001792:Blood Platelets / Q000502:physiology*; D055252:Cell-Derived Microparticles / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D046911:Macromolecular Substances; D035683:MicroRNAs; D012333:RNA, Messenger; C466422:AGO2 protein, human; C525067:MIR223, human