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 journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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