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MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1

By R. Menghini, V. Casagrande, M. Cardellini, E. Martelli, A. Terrinoni, F. Amati, M. Vasa-Nicotera, A. Ippoliti, G. Novelli, G. Melino, R. Lauro and 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. \ud \ud 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. \ud \ud 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

Topics: endothelial cells, aging, atherosclerosis, SirT1 protein, microRNAs
Publisher: American Heart Association
Year: 2009
DOI identifier: 10.1161/CIRCULATIONAHA.109.864629
OAI identifier:

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