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MicroRNA changes in human arterial endothelial cells with senescence: Relation to apoptosis, eNOS and inflammation

Rippe, Catarina LU ; Blimline, Mark; Magerko, Katherine A.; Lawson, Brooke R.; LaRocca, Thomas J.; Donato, Anthony J. and Seals, Douglas R. (2012) In Experimental Gerontology 47(1). p.45-51
Abstract
A senescent phenotype in endothelial cells is associated with increased apoptosis, reduced endothelial nitric oxide synthase (eNOS) and inflammation, which are implicated in arterial dysfunction and disease in humans. We tested the hypothesis that changes in microRNAs are associated with a senescent phenotype in human aortic endothelial cells (HAEC). Compared with early-passage HAEC, late-passage HAEC had a reduced proliferation rate and increased staining for senescence-associated beta-galactosidase and the tumor suppressor p16(INK4a). Late-passage senescent HAEC had reduced expression of proliferation-stimulating/apoptosis-suppressing miR-21, miR-214 and miR-92 and increased expression of tumor suppressors and apoptotic markers.... (More)
A senescent phenotype in endothelial cells is associated with increased apoptosis, reduced endothelial nitric oxide synthase (eNOS) and inflammation, which are implicated in arterial dysfunction and disease in humans. We tested the hypothesis that changes in microRNAs are associated with a senescent phenotype in human aortic endothelial cells (HAEC). Compared with early-passage HAEC, late-passage HAEC had a reduced proliferation rate and increased staining for senescence-associated beta-galactosidase and the tumor suppressor p16(INK4a). Late-passage senescent HAEC had reduced expression of proliferation-stimulating/apoptosis-suppressing miR-21, miR-214 and miR-92 and increased expression of tumor suppressors and apoptotic markers. eNOS-suppressing miR-221 and miR-222 were increased and eNOS protein and eNOS activation (phosphorylation at serine1177) were lower in senescent HAEC. Caveolin-1 inhibiting miR-133a was reduced and caveolin-1, a negative regulator of eNOS activity, was elevated in senescent HAEC. Inflammation-repressing miR-126 was reduced and inflammation-stimulating miR-125b was increased, whereas inflammatory proteins were greater in senescent HAEC Development of a senescent arterial endothelial cell phenotype featuring reduced cell proliferation, enhanced apoptosis and inflammation and reduced eNOS is associated with changes in miRNAs linked to the regulation of these processes. Our results support the hypothesis that miRNAs could play a critical role in arterial endothelial cell senescence. (C) 2011 Elsevier Inc. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Vascular adhesion molecule, Monocyte chemotactic protein-1, Caspase, Aging, Nitric oxide
in
Experimental Gerontology
volume
47
issue
1
pages
45 - 51
publisher
Elsevier
external identifiers
  • wos:000300123300007
  • scopus:84155170683
ISSN
1873-6815
DOI
10.1016/j.exger.2011.10.004
language
English
LU publication?
yes
id
ae47971d-ebe4-4baa-9122-c9deb6038872 (old id 2416049)
date added to LUP
2012-04-02 09:32:56
date last changed
2017-08-13 03:09:29
@article{ae47971d-ebe4-4baa-9122-c9deb6038872,
  abstract     = {A senescent phenotype in endothelial cells is associated with increased apoptosis, reduced endothelial nitric oxide synthase (eNOS) and inflammation, which are implicated in arterial dysfunction and disease in humans. We tested the hypothesis that changes in microRNAs are associated with a senescent phenotype in human aortic endothelial cells (HAEC). Compared with early-passage HAEC, late-passage HAEC had a reduced proliferation rate and increased staining for senescence-associated beta-galactosidase and the tumor suppressor p16(INK4a). Late-passage senescent HAEC had reduced expression of proliferation-stimulating/apoptosis-suppressing miR-21, miR-214 and miR-92 and increased expression of tumor suppressors and apoptotic markers. eNOS-suppressing miR-221 and miR-222 were increased and eNOS protein and eNOS activation (phosphorylation at serine1177) were lower in senescent HAEC. Caveolin-1 inhibiting miR-133a was reduced and caveolin-1, a negative regulator of eNOS activity, was elevated in senescent HAEC. Inflammation-repressing miR-126 was reduced and inflammation-stimulating miR-125b was increased, whereas inflammatory proteins were greater in senescent HAEC Development of a senescent arterial endothelial cell phenotype featuring reduced cell proliferation, enhanced apoptosis and inflammation and reduced eNOS is associated with changes in miRNAs linked to the regulation of these processes. Our results support the hypothesis that miRNAs could play a critical role in arterial endothelial cell senescence. (C) 2011 Elsevier Inc. All rights reserved.},
  author       = {Rippe, Catarina and Blimline, Mark and Magerko, Katherine A. and Lawson, Brooke R. and LaRocca, Thomas J. and Donato, Anthony J. and Seals, Douglas R.},
  issn         = {1873-6815},
  keyword      = {Vascular adhesion molecule,Monocyte chemotactic protein-1,Caspase,Aging,Nitric oxide},
  language     = {eng},
  number       = {1},
  pages        = {45--51},
  publisher    = {Elsevier},
  series       = {Experimental Gerontology},
  title        = {MicroRNA changes in human arterial endothelial cells with senescence: Relation to apoptosis, eNOS and inflammation},
  url          = {http://dx.doi.org/10.1016/j.exger.2011.10.004},
  volume       = {47},
  year         = {2012},
}