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

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Item Type:	Article
Title:	Growth arrest specific protein 6 participates in DOCA-induced target-organ damage
Creators Name:	Park, J.K., Theuer, S., Kirsch, T., Lindschau, C., Klinge, U., Heuser, A., Plehm, R., Todiras, M., Carmeliet, P., Haller, H., Luft, F.C., 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
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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