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

作     者：Ashley J. Scott Patterson Vaidehi A. Patil Lysmarie Figueroa-Rios Alexandra N. Borelli Kristyn S. Masters 

作者机构：Medical Scientist Training Program University of Wisconsin-Madison Madison WI USACellular and Molecular Biology Program University of Wisconsin-Madison Madison WI USA Department of Biomedical Engineering University of Wisconsin-Madison Madison WI USA Department of Bioengineering University of Colorado Denver | Anschutz Medical Campus Aurora CO USA Department of Biomedical Engineering University of Wisconsin-Madison Madison WI USADepartment of Bioengineering University of Colorado Denver | Anschutz Medical Campus Aurora CO USA 

出 版 物：《Journal of the Heart Valve Society》 

年 卷 期：2024年第1卷第1期

基　　金：The authors disclosed receipt of the following financial support for the research  authorship  and/or publication of this article: This work was supported by the National Heart  Lung  and Blood Institute  (grant number R01 HL172046  T32HL007936  TL1TR002375) 

主　　题：aortic valve endothelial-to-mesenchymal transition valvular interstitial cells extracellular matrix fibrosis calcification 

摘      要：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.