Cardiovascular Research Group, Vascular Biology and Metabolism, Vall d'Hebron Research Institute (VHIR), 08035 Barcelona, Spain.
Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Int J Mol Sci. 2021 Dec 24;23(1):174. doi: 10.3390/ijms23010174.
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.
关于射血分数降低的心力衰竭（HFrEF）在女性中的信息以及女性心脏衰老的潜在影响还很缺乏。我们研究了与年轻动物相比，老年雌性小鼠发生 HFrEF 的易感性，以及逆向重构的潜在差异。首先，通过异丙肾上腺素输注（30mg/kg/天，28 天）在年轻（10 周龄）和老年（22 月龄）雌性小鼠中诱导 HF。在第二组动物中，在另外 28 天的时间里，动物接受异丙肾上腺素输注后不再进行治疗。通过超声心动图、组织学和胶原 I 和胶原 III 的基因表达评估心脏重构。在异丙肾上腺素输注后，老年小鼠与年轻动物相比，除了更大的细胞肥大和组织纤维化外，还出现了类似的 HFrEF 特征。在β-肾上腺素能停药后，年轻雌性小鼠经历了 HFrEF 表型的完全逆转。相反，逆向重构在老年动物中受损，左心室射血分数、心肌细胞肥大和胶原沉积均无明显恢复。总之，慢性异丙肾上腺素输注是老年和年轻雌性小鼠 HF 的有效模型，并在两者中诱导类似的 HF 表型。与年轻动物不同，老年动物表现出逆向重构受损，即使在β-肾上腺素能停药后，仍存在持续的组织纤维化和心脏功能障碍。
