Mild transverse aortic constriction and continuous aldosterone administration induce heart failure with preserved ejection fraction.

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.