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, Massimo Federici

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1524-1532
Number of pages9
JournalCirculation
Volume120
Issue number15
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Cell Aging
MicroRNAs
Endothelial Cells
Acetylation
Nitric Oxide Synthase Type III
Human Umbilical Vein Endothelial Cells
3' Untranslated Regions
Coronary Artery Disease
Atherosclerosis
Coronary Vessels
Binding Sites
Phenotype
Therapeutics

Keywords

  • Aging
  • Atherosclerosis
  • Endothelial cells
  • MicroRNAs
  • SirT1 protein

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Menghini, R., Casagrande, V., Cardellini, M., Martelli, E., Terrinoni, A., Amati, F., ... Federici, M. (2009). MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation, 120(15), 1524-1532. https://doi.org/10.1161/CIRCULATIONAHA.109.864629

MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. / Menghini, Rossella; Casagrande, Viviana; Cardellini, Marina; Martelli, Eugenio; Terrinoni, Alessandro; Amati, Francesca; Vasa-Nicotera, Mariuca; Ippoliti, Arnaldo; Novelli, Giuseppe; Melino, Gerry; Lauro, Renato; Federici, Massimo.

In: Circulation, Vol. 120, No. 15, 10.2009, p. 1524-1532.

Research output: Contribution to journalArticle

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 2009, 'MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1', Circulation, vol. 120, no. 15, pp. 1524-1532. https://doi.org/10.1161/CIRCULATIONAHA.109.864629
Menghini R, Casagrande V, Cardellini M, Martelli E, Terrinoni A, Amati F et al. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation. 2009 Oct;120(15):1524-1532. https://doi.org/10.1161/CIRCULATIONAHA.109.864629
Menghini, Rossella ; Casagrande, Viviana ; Cardellini, Marina ; Martelli, Eugenio ; Terrinoni, Alessandro ; Amati, Francesca ; Vasa-Nicotera, Mariuca ; Ippoliti, Arnaldo ; Novelli, Giuseppe ; Melino, Gerry ; Lauro, Renato ; Federici, Massimo. / MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. In: Circulation. 2009 ; Vol. 120, No. 15. pp. 1524-1532.
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