Extracellular matrix dynamics in aortic valve health and disease: Insights into fibrocalcific remodeling and creation of biomimetic platforms

The extracellular matrix (ECM) of the aortic valve plays a pivotal role in maintaining valve function and becomes profoundly altered during the progression of calcific stenosis of the native aortic valve (CAS). CAS involves fibrocalcific ECM remodeling characterized by increased proteoglycans and glycosaminoglycans, enhanced collagen deposition, and fragmentation of elastic fibers, all of which contribute to valve thickening, fibrosis, and calcification. In this brief review, we provide an overview of these ECM changes and discuss the relationship between aberrant ECM remodeling and other pathological features of CAS - namely, differentiation of the resident valve cell types, inflammatory activity, lipid deposition, and relative hypoxia. Sexual dimorphism in ECM dynamics and the creation of disease-inspired scaffold environments to mimic CAS fibrosis are also discussed. Overall, understanding the complex interplay between cell phenotypes and ECM remodeling is crucial for elucidating the pathophysiology of CAS and developing novel treatment strategies.