title: Lipoxin A4stimulates endothelial miR-126-5p expression and its transferviamicrovesicles.
abstract: The proresolution lipid mediator lipoxin (LX)A4bestows protective bioactions on endothelial cells. We examined the impact of LXA4on transcellular endothelial signalingviamicroRNA (miR)-containing microvesicles. We report LXA4inhibition of MV release by TNF-α-treated HUVECs, associated with the down-regulation of 18 miR in endothelial microvesicles (EMVs) and the up-regulation of miR-126-5p, both in HUVECs and in EMVs. LXA4up-regulated miR-126-5p by ∼5-fold in HUVECs and promoted a release of microvesicles (LXA4-EMVs) that enhanced miR-126-5p by ∼7-fold in recipient HUVECs. In these cells, LXA4-EMVs abrogated the up-regulation of VCAM-1, induced in recipient HUVECs by EMVs released by untreated or TNF-α-treated HUVECs. LXA4-EMVs also reduced by ∼40% the expression of SPRED1, which we validated as an miR-126-5p target, whereas they stimulated monolayer repair in anin vitrowound assay. This effect was lost when the EMVs were depleted of miR-126-5p. These results provide evidence that changes in miR expression and microvesicle packaging and transfer represent a mechanism of action of LXA4, which may be relevant in vascular biology and inflammation.-Codagnone, M., Recchiuti, A., Lanuti, P., Pierdomenico, A. M., Cianci, E., Patruno, S., Mari, V. C., Simiele, F., Di Tomo, P., Pandolfi, A., Romano, M. Lipoxin A4stimulates endothelial miR-126-5p expression and its transferviamicrovesicles.
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Marilina
authors.initials: M
authors.lastname: Codagnone
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Recchiuti
authors.affiliation: Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.|Department of Medicine and Aging Science, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lanuti
authors.affiliation: Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.|Department of Medicine and Aging Science, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pierdomenico
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cianci
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Sara
authors.initials: S
authors.lastname: Patruno
authors.affiliation: Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Veronica Cecilia
authors.initials: VC
authors.lastname: Mari
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Felice
authors.initials: F
authors.lastname: Simiele
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Pamela
authors.initials: P
authors.lastname: Di Tomo
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Assunta
authors.initials: A
authors.lastname: Pandolfi
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; mromano@unich.it.|Center on Aging Science and Translational Medicine (CeSI-MeT), G. D'Annunzio University of Chieti-Pescara, Chieti, Italy; and.
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
mesh_terms: D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D044045:Lipoxins / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D044045:Lipoxins; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C040527:lipoxin A4
keywords: inflammation; intercellular signaling; microRNA; proresolving mediators; vascular repair