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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-7-23
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pubmed:abstractText |
Growth arrest-specific protein 6 (Gas 6) is involved in inflammatory kidney diseases, vascular remodeling, cell adhesion, and thrombus formation. We explored a role for Gas 6 in aldosterone-induced target organ damage. We observed that Gas 6 was upregulated in rats with high aldosterone levels. Mineralocorticoid receptor blockade prevented target organ damage and decreased the elevated Gas 6 expression. Vascular smooth muscle cells given aldosterone increased their Gas 6 expression in vitro. To test the pathophysiological relevance, we investigated the effects of deoxycorticosterone acetate (DOCA) on Gas 6 gene-deleted ((-/-)) mice. After 6 weeks DOCA, Gas 6(-/-) mice developed similar telemetric blood pressure elevations compared to wild-type mice but were protected from cardiac hypertrophy. Cardiac expression of interleukin 6 and collagen IV was blunted in Gas 6(-/-) mice, indicating reduced inflammation and fibrosis. Gas 6(-/-) mice also had an improved renal function with reduced albuminuria, compared to wild-type mice. Renal fibrosis and fibronectin deposition in the kidney were also reduced. Gas 6 deficiency reduces the detrimental effects of aldosterone on cardiac and renal remodeling independent of blood pressure reduction. Gas 6 appears to play a role in mineralocorticoid receptor-mediated target organ damage. Furthermore, because warfarin interferes with Gas 6 protein expression, the findings could be of clinical relevance for anticoagulant choices.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1524-4563
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pubmed:author |
pubmed-author:CarmelietPeterP,
pubmed-author:FiebelerAnetteA,
pubmed-author:HallerHermannH,
pubmed-author:HeuserArndA,
pubmed-author:KirschTorstenT,
pubmed-author:KlingeUweU,
pubmed-author:LindschauCarstenC,
pubmed-author:LuftFriedrich CFC,
pubmed-author:MullerDominik NDN,
pubmed-author:ParkJoon-KeunJK,
pubmed-author:PlehmRalphR,
pubmed-author:TheuerStefanieS,
pubmed-author:TodirasMihaiM
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pubmed:issnType |
Electronic
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
359-64
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19564549-Acute Kidney Injury,
pubmed-meshheading:19564549-Albuminuria,
pubmed-meshheading:19564549-Aldosterone,
pubmed-meshheading:19564549-Analysis of Variance,
pubmed-meshheading:19564549-Animals,
pubmed-meshheading:19564549-Blood Pressure,
pubmed-meshheading:19564549-Cardiomegaly,
pubmed-meshheading:19564549-Cells, Cultured,
pubmed-meshheading:19564549-Desoxycorticosterone,
pubmed-meshheading:19564549-Disease Models, Animal,
pubmed-meshheading:19564549-Gene Expression Regulation,
pubmed-meshheading:19564549-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:19564549-Kidney,
pubmed-meshheading:19564549-Mice,
pubmed-meshheading:19564549-Mice, Knockout,
pubmed-meshheading:19564549-Muscle, Smooth, Vascular,
pubmed-meshheading:19564549-Probability,
pubmed-meshheading:19564549-Random Allocation,
pubmed-meshheading:19564549-Rats,
pubmed-meshheading:19564549-Rats, Sprague-Dawley,
pubmed-meshheading:19564549-Species Specificity
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pubmed:year |
2009
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pubmed:articleTitle |
Growth arrest specific protein 6 participates in DOCA-induced target-organ damage.
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pubmed:affiliation |
Robert-Rössle-Str 10, 13125 Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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