| First Author | López-Andrés N | Year | 2011 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 301 |
| Issue | 6 | Pages | H2372-82 |
| PubMed ID | 21926338 | Mgi Jnum | J:179108 |
| Mgi Id | MGI:5301073 | Doi | 10.1152/ajpheart.00283.2011 |
| Citation | Lopez-Andres N, et al. (2011) A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone. Am J Physiol Heart Circ Physiol 301(6):H2372-82 |
| abstractText | Hyperaldosteronim is associated with left ventricular (LV) hypertrophy (LVH) and fibrosis. Cardiotrophin (CT)-1 is a cytokine that induces myocardial remodeling. We investigated whether CT-1 mediates aldosterone (Aldo)-induced myocardial remodeling in two experimental models. Wistar rats were treated with Aldo-salt (1 mg.kg(-1).day(-1)) with or without spironolactone (200 mg.kg(-1).day(-1)) for 3 wk. Wild-type (WT) and CT-1-null mice were infused with Aldo (1 mg.kg(-1).day(-1)) for 3 wk. Hemodynamic parameters were analyzed. LVH, fibrosis, inflammation, and CT-1 expression were evaluated in both experimental models by histopathological analysis, RT-PCR, Western blot analysis, and ELISA. Hypertensive Aldo-treated rats exhibited increased LV end-diastolic pressure and -dP/dt compared with controls. The cardiac index, LV cross-sectional area and wall thickness, cardiomyocyte size, collagen deposition, and inflammation were increased in Aldo-salt-treated rats. Myocardial expression of molecular markers assessing LVH and fibrosis as well as CT-l levels were also augmented by Aldo-salt. Spironolactone treatment reversed all the above effects. CT-1 correlated positively with hemodynamic, histological, and molecular parameters showing myocardial remodeling. In WT and CT-1-null mice, Aldo infusion did not modify blood pressure. Whereas Aldo treatment induced LVH, fibrosis, and inflammation in WT mice, the mineralocorticoid did not provoke cardiac remodeling in CT-1-null mice. In conclusion, in experimental hyperaldosteronism, the increase in CT-1 expression was associated with parameters showing LVH and fibrosis. CT-1-null mice were resistant to Aldo-induced LVH and fibrosis. These data suggest a key role for CT-1 in cardiac remodeling induced by Aldo independent of changes in blood pressure levels. |
