Author:
Ahmed Suhail,Kurusamy Sathishkumar,David Ezra Leander Santhosh,Khan Kinza,Kalyanakrishnan Krithika,Ian-Gobo Miebaka,Kola Teja Manidhar,Wilkinson Robert N.,Kannappan Vinodh,Wang Weiguang,Gómez Manuel J.,Redondo Juan Miguel,Cotton James,Armesilla Angel L.
Abstract
AbstractAngiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a expression in endothelial cells during blood vessel formation have reported conflicting results. Here, we have assessed the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. Transfection of miR-133a-3p or -5p mimics in primary human endothelial cells significantly inhibited proliferation, migration, and tubular morphogenesis of transfected cells. Screening of gene arrays related to angiogenic processes, and further validation by TaqMan qPCR, revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a collection of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. Our results suggest that controlled delivery of miR-133a-3p mimics, or antagomirs in diseased endothelial cells, might open new therapeutic interventions to treat patients suffering from cardiovascular pathologies that occur with excessive or insufficient angiogenesis.
Funder
Pro-CNIC Foundation
“la Caixa” Foundation
Ministerio de Ciencia en Innovacion, Spain
Instituto de Salud Carlos III
Ministerio de Economia, Industria y Competitividad, Spain
Wolverhampton Coronary Aftercare Support Group
Rotha Abraham Bequest
Research Institute in Healthcare Sciences
Publisher
Springer Science and Business Media LLC
Cited by
4 articles.
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