Why the study?
Mechanisms underlying cardiac remodeling in aortic valvular disease remain poorly understood, partially due to a lack of appropriate preclinical animal models.
Trans-apical wire destruction of the aortic valve is an efficient method to generate a murine model of aortic regurgitation with subsequent eccentric LV hypertrophy and heart failure.
New murine AR model enables mechanistic valvular studies; leaves open human translation pending validation.
Background The mechanisms underlying cardiac remodeling in aortic valvular (AoV) disease remain poorly understood, partially due to the insufficiency of appropriate preclinical animal models. Here, we present a novel murine model of aortic regurgitation (AR) generated by trans‐apical wire destruction of the AoV. Methods Directed by echocardiography, apical puncture of the left ventricle (LV) was performed in adult male C57BL/6 mice, and a metal guidewire was used to induce AoV destruction. Echocardiography, invasive LV hemodynamic and histological examination were conducted to assess the degree of AR, LV function and remodeling. Results AR mice exhibited rapid aortic regurgitation velocity (424 ± 15.22 mm/s) immediately following successful surgery. Four weeks post‐surgery, echocardiography revealed a 54.6% increase in LV diastolic diameter and a 55.1% decrease in LV ejection fraction in AR mice compared to sham mice. Pressure‐volume catheterization indicated that AR mice had significantly larger LV end‐diastolic volumes (66.2 ± 1.5 μL vs. 41.8 ± 3.4 μL), reduced LV contractility (lower dP/dt max and Ees), and diminished LV compliance (smaller dP/dt min and longer Tau) compared to sham mice. Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue, as well as a 107% and a 122% increase of heart weight/tibial length and lung weight/tibial length, respectively, relative to sham mice. Conclusions The trans‐apex wire‐induced destruction of the AoV establishes a novel and efficient murine model to develop AR, characterized by significant eccentric LV hypertrophy, heart failure, and pulmonary congestion.
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Huang et al. (2025) studied this question.
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