Preclinical Mouse Models in Calcific Aortic Valve Disease: Bridging Pathophysiology and Therapeutic Innovation

Abstract

Calcific aortic valve disease (CAVD) is a progressive condition characterized by leaflet thickening, inflammation, lipid accumulation, and calcification, ultimately leading to aortic stenosis and impaired cardiac function. Despite clinical similarities to atherosclerosis, CAVD exhibits distinct pathophysiological features, and currently, no effective pharmacological therapy exists. Given the limitations of human clinical trials and in vitro models, a diverse array of genetically engineered and diet-induced mouse models have been developed to explore the disease’s mechanisms and evaluate potential treatments. These include models targeting lipid metabolism (e.g., ApoE-/-, LDLr-/-), developmental signaling (e.g., NOTCH1+/-), inflammation (e.g., IL-1Ra-/-), and extracellular matrix remodeling (e.g., MGP-/-, Fibulin-4 deficient). Emerging surgical and dietary models further expand the toolkit for translational research. Collectively, these models have enhanced our understanding of disease progression and offered platforms to test experimental therapies, highlighting the dynamic and multifactorial nature of CAVD.