| First Author | Park JK | Year | 2009 |
| Journal | Hypertension | Volume | 54 |
| Issue | 2 | Pages | 359-64 |
| PubMed ID | 19564549 | Mgi Jnum | J:164950 |
| Mgi Id | MGI:4835818 | Doi | 10.1161/HYPERTENSIONAHA.109.129460 |
| Citation | Park JK, et al. (2009) Growth arrest specific protein 6 participates in DOCA-induced target-organ damage. Hypertension 54(2):359-64 |
| 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. |
