Abstract
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.
Highlights
Introduction distributed under the terms andHeart failure (HF) is a major public health problem associated with high morbidity and mortality, in the aging population [1]
Reduced ejection fraction (HFrEF), younger age is associated with greater improvement of ventricular function after pharmacological or device therapy or after left ventricular assist device (LVAD) support [4,5]
As expected in the young population, isoproterenol infusion induced a considerable increase in both diastolic and systolic left ventricle (LV) dimensions and marked reductions in ejection fraction and fractional shortening, changes that were not observed in the sham group (Figure 1, solid bars)
Summary
Heart failure (HF) is a major public health problem associated with high morbidity and mortality, in the aging population [1]. HF prevalence increases with age, with 2% of affected individuals in the general population and up to >8% of those aged ≥75 years [2,3]. Aging worsens HF prognosis, having been independently associated with increased readmission and mortality rates [3]. Several factors have been advocated to explain the different behavior of HF according to age, such as the coexistence of comorbidities, the loss of functional exercise capacity and, more importantly, the presence of aging-associated vascular, cellular and interstitial molecular changes at the cardiac level that result in stiffer and less compliant hearts with greater vulnerability to functional decline [6,7]
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