Key result
Mild TAC plus aldosterone induces comprehensive HFpEF phenotypes with diastolic dysfunction and exercise intolerance in mice.
Why the study?
HFpEF pathophysiology remains poorly understood partly due to the lack of reliable animal models.
Does mild transverse aortic constriction combined with continuous aldosterone administration induce a heart failure with preserved ejection fraction phenotype in mice?
Does mild transverse aortic constriction combined with continuous aldosterone administration induce a heart failure with preserved ejection fraction phenotype in mice?
Mild transverse aortic constriction combined with continuous aldosterone administration successfully reproduces key features of HFpEF pathophysiology in mice, providing a valuable model for future mechanistic and therapeutic studies.
Answers are grounded in this paper and cite their sources.
This aldosterone-TAC mouse model may enable preclinical HFpEF studies; human translation remains unproven.
The mechanisms of heart failure with preserved ejection fraction (HFpEF) remain poorly understood, partly due to the lack of reliable animal models. We aimed to establish a more adaptable HFpEF model by focusing on pressure overload-induced hypertrophy and neurohumoral factors. Mild transverse aortic constriction (TAC) using a 25G needle or a sham operation was performed on C57BL/6 mice. One week later, aldosterone (2 μg/mouse/day) or vehicle was administered subcutaneously via osmotic minipumps. Four weeks later, echocardiography was performed, followed by tissue collection. Echocardiography showed a significant increase in left ventricular (LV) mass in the TAC and aldosterone (TAC+Ald) group compared with controls. In treadmill testing, the TAC+Ald group exhibited significantly reduced running distance. Pressure–volume loop analysis revealed an elevated end-diastolic pressure–volume relationship, indicating LV diastolic dysfunction. Both LV and lung weights were significantly increased, indicating LV hypertrophy and pulmonary congestion. Histology showed a greater cardiomyocyte cross-sectional area in the TAC+Ald group. Additionally, expression levels of fibrosis- and hypertrophy-related genes were significantly upregulated. In conclusion, the TAC+Ald model reproduces key features of HFpEF pathophysiology and may serve as a valuable platform for mechanistic and therapeutic studies. • HFpEF pathophysiology remains poorly understood due to lack of reliable models. • Mild TAC combined with aldosterone induces HFpEF phenotypes in C57BL/6J mice. • The model shows diastolic dysfunction, hypertrophy, pulmonary congestion, and reduced exercise capacity. • Provides a valuable tool to study HFpEF pathophysiology and potential treatments.
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Hanatani et al. (2025) studied Heart failure with preserved ejection fraction (HFpEF). Mild transverse aortic constriction (TAC) and aldosterone vs. Sham operation and vehicle was evaluated on HFpEF phenotypes (LV mass, running distance, diastolic dysfunction). Mild transverse aortic constriction combined with aldosterone induced HFpEF phenotypes, including diastolic dysfunction, hypertrophy, pulmonary congestion, and reduced exercise capacity in mice.
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