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Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/7850

Title: MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1
Authors: Menghini, R.
Casagrande, V.
Cardellini, M.
Martelli, E.
Terrinoni, A.
Amati, F.
Vasa-Nicotera, M.
Ippoliti, A.
Novelli, G.
Melino, G.
Lauro, R.
Federici, M.
Issue Date: Oct-2009
Publisher: American Heart Association
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.
Abstract: 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.
ISSN: 0009-7322
Links: http://dx.doi.org/10.1161/CIRCULATIONAHA.109.(...)
http://hdl.handle.net/2381/7850
Type: Article
Description: This is the author’s final draft of the paper. The final published version is available at the DOI below:
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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