title: A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone.
abstract: 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.
authors.affiliation: U, Faculty of Medicine, Institut National de la Santé et de la Recherche Médicale, Vandoeuvre-lès-Nancy, France. natalia.lopez-andres@nancy.inserm.fr
authors.forename: Natalia
authors.initials: N
authors.lastname: López-Andrés
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martin-Fernandez
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Fortuno
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
mesh_terms: D000450:Aldosterone; D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D006339:Heart Rate; D006929:Hyperaldosteronism / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary; D013148:Spironolactone / Q000494:pharmacology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000451:Mineralocorticoid Receptor Antagonists; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D000450:Aldosterone; D003094:Collagen; C092073:cardiotrophin 1