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Growth arrest specific protein 6 participates in DOCA-induced target-organ damage

Item Type:Article
Title:Growth arrest specific protein 6 participates in DOCA-induced target-organ damage
Creators Name:Park, J.K. and Theuer, S. and Kirsch, T. and Lindschau, C. and Klinge, U. and Heuser, A. and Plehm, R. and Todiras, M. and Carmeliet, P. and Haller, H. and Luft, F.C. and Mueller, D.N. and Fiebeler, A.
Abstract: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.
Keywords:Gas 6, Aldosterone, Cardiac Hypertrophy, Albuminuria, Inflammation, Animals, Mice, Rats
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:54
Number:2
Page Range:359-364
Date:August 2009
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.109.129460
PubMed:View item in PubMed

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