Paper Title
Elevated Serum Aldosterone Levels in Pressure Overloaded Mice Induced Sgk1 in Cardiomyocytes But it was Not Involved In 2, 5-Dimethylcelecoxib’s Action

We previously reported that pressure overload by transverse aortic constriction (TAC) induced cardiac remodeling and heart failure in mice and the celecoxib analogue 2,5-dimethylcelecoxib (DM-celecoxib), which does not inhibit COX-2, showed therapeutic effect. However, TAC operation might elevate aldosterone level and it could be involved in cardiac remodeling and related to DM-celecoxib’s mechanism of action. In the present study, therefore, we examined the serum aldosterone concentration, its effect on heart and its relation to DM-celecoxib’s action using TAC-operated mice. Eight to ten weeks old male C57BL/6 mice were subjected to TAC for 4 weeks with or without DM-celecoxib treatment. Functional and morphological measurements showed that TAC operation induced cardiac hypertrophy, impaired left ventricular systolic function, and increased interstitial fibrotic area and cardiomyocyte size. TAC operation significantly increased the serum level of aldosterone. Since aldosterone binds to mineral corticoid receptor (MR) and induces serum and glucocorticoid inducible kinase 1 (SGK1), we measured the expression levels of MR and SGK1 in the mouse heart. We found that SGK1 expression level was significantly increased in TAC-operated mouse hearts without significant change in MR expression level. However, DM-celecoxib treatment did not affect either aldosterone level or aldosterone-induced gene expressions. These results suggest that aldosterone might play an important role in cardiac hypertrophy induced by pressure overload, but the effect of DM-celecoxib on cardiac remodeling may be independent of serum aldosterone action.