A novel mouse model for mineral homeostasis disrupting induced calcific aortic valve stenosis

Abstract

Abstract Background Calcific aortic valve disease (CAVD) is the most common valve disease that has been occurring with rapidly increasing morbidity. Chronic kidney disease (CKD) which disrupts mineral homeostasis due the impaired renal function, is one of the known factors, largely contributing to risk of CAVD, independent of atherosclerosis. To the best of our knowledge, there are few calcific aortic valve stenosis mouse models simulating conditions under CKD that develop hemodynamically significant stenosis as well as calcification, Purpose The purpose was to assess the feasibility to develop a mouse model of CAVD considering risks under CKD. Methods For this model, C57/BL6 mice were firstly underwent aortic valve wire injury by spring guidewires inserting into left ventricle via right common carotid artery. Vitamin D was subcutaneous injected on 3 consecutive days from the second day of aortic valve wire injury. Echocardiography was performed to evaluate aortic valve function at 7, 14 and 28 days. Then the mice were sacrificed and aortic valves were collected to make histological analysis. Results An obvious increase in aortic velocity was already observed at 7 days after injury by continuous echocardiographic assessment and remained stable from 14 days compared with sham mice. Alizarin red staining showed calcium nodules formation in valve leaflets 14 days after injury and became more conspicuous at 28 days. Aortic valve thickening, increased macrophage infiltration, fibrosis and remarkable osteogenic markers were found in aortic valves at 28 days after injury. Conclusions We develop a novel mouse model of CAVD, especially simulating risks under CKD and mineral homeostasis disrupting. This model may be a convenient and valuable tool to investigate the mechanism of CAVD and further explore potential therapeutic strategies.Fig1.Alizarin red staining aortic valvesFig2.Immunostaining of aortic valves