On the shape and structure of the murine pulmonary heart valve

Murine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. We also observed that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.