In calcific aortic valve disease, fibrotic and calcific lesions form focally in the fibrosa layer of the valve leaflets. Layer-specific pathosusceptibility suggests that the fibrosa microenvironment is permissive to pathological development. The cellular microenvironment in the aortic valve is defined by a variety of biomechanical-, biochemical-, and extracellular-mediated factors, some of which are unique to the fibrosa. Growing evidence supports the role of these microenvironmental cues in the local regulation of side-specific valve cell phenotypes and focal pathological alterations, revealing new insights into the cellular and molecular processes that contribute to calcific aortic valve disease.
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