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MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1

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posted on 2010-04-29, 12:35 authored by R. Menghini, V. Casagrande, M. Cardellini, E. Martelli, A. Terrinoni, F. Amati, M. Vasa-Nicotera, A. Ippoliti, G. Novelli, G. Melino, R. Lauro, M. Federici
Background: Aging is a major risk factor for the development of atherosclerosis and coronary artery disease. Through a microarray approach, we have identified a microRNA (miR-217) that is progressively expressed in endothelial cells with aging. miR-217 regulates the expression of silent information regulator 1 (SirT1), a major regulator of longevity and metabolic disorders that is progressively reduced in multiple tissues during aging. Methods and Results: miR-217 inhibits SirT1 expression through a miR-217–binding site within the 3'-UTR of SirT1. In young human umbilical vein endothelial cells, human aortic endothelial cells, and human coronary artery endothelial cells, miR-217 induces a premature senescence-like phenotype and leads to an impairment in angiogenesis via inhibition of SirT1 and modulation of FoxO1 (forkhead box O1) and endothelial nitric oxide synthase acetylation. Conversely, inhibition of miR-217 in old endothelial cells ultimately reduces senescence and increases angiogenic activity via an increase in SirT1. miR-217 is expressed in human atherosclerotic lesions and is negatively correlated with SirT1 expression and with FoxO1 acetylation status. Conclusions: Our data pinpoint miR-217 as an endogenous inhibitor of SirT1, which promotes endothelial senescence and is potentially amenable to therapeutic manipulation for prevention of endothelial dysfunction in metabolic disorders.

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Citation

MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1. Rossella Menghini, Viviana Casagrande, Marina Cardellini, Eugenio Martelli, Alessandro Terrinoni, Francesca Amati, Mariuca Vasa-Nicotera, Arnaldo Ippoliti, Giuseppe Novelli, Gerry Melino, Renato Lauro and Massimo Federici. Circulation 2009;120;1524-1532.

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MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1. Rossella Menghini

Publisher

American Heart Association

issn

0009-7322

Available date

2010-04-29

Publisher version

http://circ.ahajournals.org/content/120/15/1524

Language

en

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