title: Inhibition of microRNA-125a promotes human endothelial cell proliferation and viability through an antiapoptotic mechanism.
abstract: The microRNA-125a (miR-125a) is highly expressed in endothelial cells, but its role in vascular biology is not known. Endothelial cell proliferation and viability play an important role in endothelial healing, and we hypothesize that miR-125a regulates this process. The aim of the present study was to investigate if miR-125a controls human endothelial cell proliferation, viability and endothelial healing, and to assess the mechanisms involved. We showed that overexpression of miR-125a by transfection with miR-125a mimic reduced human umbilical vein endothelial cell (HUVEC) proliferation and viability, and stimulated apoptosis as demonstrated by a miR-125a-induced increase of the proportion of annexin V-positive cells monitored by flow cytometry. Moreover, we showed that the miR-125a mimic downregulated the antiapoptotic Bcl2 protein and upregulated caspase 3, suggesting that these two proteins represent molecular targets for miR-125a. Accordingly, transfection with miR-125a inhibitor, downregulating miR-125a expression, promoted HUVEC proliferation and viability, and reduced apoptosis. Importantly, transfection with miR-125a inhibitor promoted HUVEC tube formation in Matrigel, suggesting that reduction of miR-125a has a proangiogenic effect. In conclusion, downregulation of miR-125a through local transfection with miR-125a inhibitor might be a new way to enhance endothelial cell proliferation and viability, thereby promoting the reendothelialization observed in response to intimal injury.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Svensson
authors.forename: Olof
authors.initials: O
authors.lastname: Gidlöf
authors.forename: Karolina M
authors.initials: KM
authors.lastname: Turczyńska
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
authors.forename: Bengt-Olof
authors.initials: BO
authors.lastname: Nilsson
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3