Abstract: Objective To investigate the optimal time window for observation of catheter-induced valve injury that mimics calcified aortic valve disease in mice. Methods A catheter was inserted into the right common carotid artery of 8-week-old C57BL6 mice under ultrasound guidance, and aortic valve injury was induced using the guide wire. At 4, 8 and 16 weeks after modeling, the mice were subjected to ultrasound measurement of the heart short axial shortening rate, aortic valve peak velocity and aortic valve orifice area. Grain-Eosin staining was used to observe the changes in the thickness of the aortic valve, and calcium deposition in the aortic valve was assessed using Alizarin red staining. Immunofluorescence assay was performed to detect the expression of alkaline phosphatase (ALP) in the aortic valve. Results At 4, 8 and 16 weeks after modeling, valve thickness (P=0.002), calcium deposition (P<0.0001) and the expression of osteogenic protein ALP (P=0.0016) were significantly increased, but their increments were comparable at the 3 time points of observation. Conclusion In mouse models of calcific aortic valve disease induced by catheter valve injury, 4 weeks after the injury appears to be the optimal time window for observation of pathophysiological changes in the aortic valves to avoid further increase of the death rate of the mice over time.

Key words: calcific aortic valve disease; mouse model; catheter injury