A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone
| Autor: | Faiez Zannad, Victoria Cachofeiro, M.A. Fortuño, Javier Díez, Beatriz Martín-Fernández, Patrick Rossignol, Vicente Lahera, Natalia López-Andrés |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Physiology Blood Pressure Spironolactone Left ventricular hypertrophy Ventricular Function Left Muscle hypertrophy chemistry.chemical_compound Mice Fibrosis Heart Rate Aldosterone Mineralocorticoid Receptor Antagonists Mice Knockout Ventricular Remodeling Hypertension Ventricular pressure Cytokines Hypertrophy Left Ventricular Collagen Inflammation Mediators Cardiology and Cardiovascular Medicine endocrine system medicine.medical_specialty Cardiotrophin 1 medicine.drug_class Blotting Western Enzyme-Linked Immunosorbent Assay Real-Time Polymerase Chain Reaction Physiology (medical) Internal medicine Hyperaldosteronism medicine Ventricular Pressure Animals Rats Wistar Sodium Chloride Dietary Ventricular remodeling Inflammation business.industry Myocardium medicine.disease Rats Mice Inbred C57BL Disease Models Animal Endocrinology chemistry Mineralocorticoid business |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 301(6) |
| ISSN: | 1522-1539 |
| Popis: | 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/d t 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. |
| Databáze: | OpenAIRE |
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