Linked Life Data

20881255

Source:http://linkedlifedata.com/resource/pubmed/id/20881255

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-11-24
pubmed:abstractText
The IGF-I pathway and renin-angiotensin-aldosterone axis are both involved in the pathogenesis of hypertension and atherosclerosis, but no information is available about IGF-I and aldosterone interaction or their potential synergistic effects in vascular smooth muscle cells (VSMCs). The aims of this study were to investigate whether aldosterone influences IGF-I signaling and to determine the mechanism(s) by which aldosterone affects IGF-I function. Aldosterone resulted in significant increases in the Akt (1.87 ± 0.24, P < 0.001), MAPK (1.78 ± 0.13, P < 0.001), p70S6kinase (1.92 ± 0.15, P < 0.001), IGF-I receptor (1.69 ± 0.05, P < 0.01), and insulin receptor substrate-1 (1.7 ± 0.04, P < 0.01) (fold increase, mean ± SEM, n = 3) phosphorylation responses to IGF-I compared with IGF-I treatment alone. There were also significant increases in VSMC proliferation, migration, and protein synthesis (1.63 ± 0.03-, 1.56 ± 0.08-, and 1.51 ± 0.04-fold increases compared with IGF-I alone, respectively, n = 3, P < 0.001). Aldosterone induced osteopontin (OPN) mRNA expression and activation of ?V?3-integrin as well as an increase in the synthesis of IGF-I receptor. The enhancing effects of aldosterone were inhibited by eplerenone (10 ?mol/liter), actinomycin-D (20 nmol/liter), and an anti-?V?3-integrin antibody that blocks OPN binding. The antioxidant N-acetylcysteine (2 mmol/liter) completely inhibited the ability of aldosterone to induce any of these changes. In conclusion, our results show that aldosterone enhances IGF-I signaling and biological actions in VSMCs through induction of OPN followed by its subsequent activation of the ?V?3-integrin and by increasing IGF-I receptor. These changes are mediated in part through increased oxidative stress. The findings suggest a new mechanism by which aldosterone could accelerate the development of atherosclerosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5851-64
pubmed:meshHeading
pubmed-meshheading:20881255-Aldosterone, pubmed-meshheading:20881255-Animals, pubmed-meshheading:20881255-Aorta, pubmed-meshheading:20881255-Cell Movement, pubmed-meshheading:20881255-Cell Proliferation, pubmed-meshheading:20881255-Cells, Cultured, pubmed-meshheading:20881255-Insulin-Like Growth Factor I, pubmed-meshheading:20881255-Integrin alphaVbeta3, pubmed-meshheading:20881255-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:20881255-Muscle, Smooth, Vascular, pubmed-meshheading:20881255-Myocytes, Smooth Muscle, pubmed-meshheading:20881255-Osteopontin, pubmed-meshheading:20881255-Phosphorylation, pubmed-meshheading:20881255-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20881255-Ribosomal Protein S6 Kinases, 70-kDa, pubmed-meshheading:20881255-Signal Transduction, pubmed-meshheading:20881255-Swine
pubmed:year
2010
pubmed:articleTitle
Aldosterone enhances IGF-I-mediated signaling and biological function in vascular smooth muscle cells.
pubmed:affiliation
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural