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. (Circulation. 2009;120:1524-1532.)

Menghini, R., Casagrande, V., Cardellini, M., Martelli, E., Terrinoni, A., Amati, F., et al. (2009). MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. CIRCULATION, 120(15), 1524-1532 [10.1161/CIRCULATIONAHA.109.864629].

MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1

MENGHINI, ROSSELLA;CARDELLINI, MARINA;MARTELLI, EUGENIO;Terrinoni, A;AMATI, FRANCESCA;IPPOLITI, ARNALDO;NOVELLI, GIUSEPPE;MELINO, GENNARO;LAURO, RENATO;FEDERICI, MASSIMO
2009-01-01

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. (Circulation. 2009;120:1524-1532.)
2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - MEDICINA INTERNA
Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITA' MOTORIE
English
Con Impact Factor ISI
endothelial cells; aging; atherosclerosis; SirT1 protein; microRNAs
Menghini, R., Casagrande, V., Cardellini, M., Martelli, E., Terrinoni, A., Amati, F., et al. (2009). MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. CIRCULATION, 120(15), 1524-1532 [10.1161/CIRCULATIONAHA.109.864629].
Menghini, R; Casagrande, V; Cardellini, M; Martelli, E; Terrinoni, A; Amati, F; Vasa Nicotera, M; Ippoliti, A; Novelli, G; Melino, G; Lauro, R; Federi...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39005
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