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 language | English |
|---|---|
| Pages (from-to) | 1524-1532 |
| Number of pages | 9 |
| Journal | Circulation |
| Volume | 120 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Oct 2009 |
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Keywords
- Aging
- Atherosclerosis
- Endothelial cells
- MicroRNAs
- SirT1 protein
ASJC Scopus subject areas
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1
AU - Menghini, Rossella
AU - Casagrande, Viviana
AU - Cardellini, Marina
AU - Martelli, Eugenio
AU - Terrinoni, Alessandro
AU - Amati, Francesca
AU - Vasa-Nicotera, Mariuca
AU - Ippoliti, Arnaldo
AU - Novelli, Giuseppe
AU - Melino, Gerry
AU - Lauro, Renato
AU - Federici, Massimo
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Aging
KW - Atherosclerosis
KW - Endothelial cells
KW - MicroRNAs
KW - SirT1 protein
UR - http://www.scopus.com/inward/record.url?scp=70350134022&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350134022&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.109.864629
DO - 10.1161/CIRCULATIONAHA.109.864629
M3 - Article
C2 - 19786632
AN - SCOPUS:70350134022
VL - 120
SP - 1524
EP - 1532
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 15
ER -