Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy

International Journal of Molecular Sciences

Marta Tajes¹  Laia Yáñez-Bisbe²  Javier Inserte²  Antonio Rodríguez-Sinovas²  Marisol Ruiz-Meana²  Begoña Benito²  Núria Farré³  Anna Garcia-Elias⁴  Ramón Farré⁵  Isaac Almendros⁵ 

[1] Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain;Cardiovascular Research Group, Vascular Biology and Metabolism, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain;Department of Cardiology, Hospital del Mar, 08003 Barcelona, Spain;Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain;Unit of Biophysics and Bioengineering, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain;

关键词: heart failure;    HFrEF;    ageing;    cardiac remodeling;    ventricular dysfunction;    reverse remodeling;   

DOI  :  10.3390/ijms23010174

来源: DOAJ

【 摘 要 】

Information about heart failure with reduced ejection fraction (HFrEF) in women and the potential effects of aging in the female heart is scarce. We investigated the vulnerability to develop HFrEF in female elderly mice compared to young animals, as well as potential differences in reverse remodeling. First, HF was induced by isoproterenol infusion (30 mg/kg/day, 28 days) in young (10-week-old) and elderly (22-month-old) female mice. In a second set of animals, mice underwent isoproterenol infusion followed by no treatment during 28 additional days. Cardiac remodeling was assessed by echocardiography, histology and gene expression of collagen-I and collagen-III. Following isoproterenol infusion, elderly mice developed similar HFrEF features compared to young animals, except for greater cell hypertrophy and tissue fibrosis. After beta-adrenergic withdrawal, young female mice experienced complete reversal of the HFrEF phenotype. Conversely, reversed remodeling was impaired in elderly animals, with no significant recovery of LV ejection fraction, cardiomyocyte hypertrophy and collagen deposition. In conclusion, chronic isoproterenol infusion is a valid HF model for elderly and young female mice and induces a similar HF phenotype in both. Elderly animals, unlike young, show impaired reverse remodeling, with persistent tissue fibrosis and cardiac dysfunction even after beta-adrenergic withdrawal.

【 授权许可】

Unknown