title: Platelet-secreted microRNA-223 promotes endothelial cell apoptosis induced by advanced glycation end products via targeting the insulin-like growth factor 1 receptor.
abstract: Platelets play a significant role in atherosclerosis, stroke, and asthma through active interaction with neutrophils, monocytes, and vascular endothelial cells. The mechanism underlying these intercellular interactions, however, is incompletely understood. In this study, we report that platelets can remotely modulate vascular endothelial cell apoptosis through releasing microRNA-223 (miR-223)-containing microvesicles (MVs). First, platelets expressed abundant miRNAs, and miR-223 had the highest level of expression. Platelet miR-223 and other miRNAs can be upregulated by the stimulation with thrombopoietin (TPO) or thrombin. Unlike leukocytes, platelets contained high levels of pre-miRNAs, and upregulation of mature platelet miRNAs by TPO was correlated with decreased pre-miRNAs. Second, under stimulation with TPO, platelets released a large amount of MVs, which also contain higher levels of miR-223. Elevation of miR-223 inside circulating platelet MVs (P-MVs) was also observed in plasma samples from patients with enteritis, hepatitis, nephritis, or atherosclerosis. Third, incubation of P-MVs with HUVECs, which had significantly lower levels of miR-223 than platelets, showed that P-MVs effectively delivered miR-223 into HUVECs. Finally, in HUVECs, exogenous platelet miR-223 decreased the level of insulin-like growth factor 1 receptor and thus promoted HUVEC apoptosis induced by advanced glycation end products. The proapoptotic effect of P-MVs on HUVECs was largely abolished by depleting cellular miR-223 using anti-miR-223 antisense oligonucleotide. In conclusion, our study presents the first evidence, to our knowledge, that platelet-released miR-223 promotes advanced glycation end product-induced vascular endothelial cell apoptosis via targeting insulin-like growth factor 1 receptor.
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu 210093, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Donghai
authors.initials: D
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001692:Biological Transport; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D017127:Glycation End Products, Advanced; D035683:MicroRNAs; D012322:RNA Precursors; D017526:Receptor, IGF Type 1; D013926:Thrombopoietin; C525067:MIR223, human