Perspectives on pediatric congenital aortic valve stenosis: Extracellular matrix proteins, post translational modifications, and proteomic strategies

In heart valve biology, organization of the extracellular matrix structure is directly correlated to valve function. This is especially true in cases of pediatric congenital aortic valve stenosis (pCAVS), in which extracellular matrix (ECM) dysregulation is a hallmark of the disease, eventually leading to left ventricular hypertrophy and heart failure. Therapeutic strategies are limited, especially in pediatric cases in which mechanical and tissue engineered valve replacements may not be a suitable option. By identifying mechanisms of translational and post-translational dysregulation of ECM in CAVS, potential drug targets can be identified, and better bioengineered solutions can be developed. In this review, we summarize current knowledge regarding ECM proteins and their post translational modifications (PTMs) during aortic valve development and disease and contributing factors to ECM dysregulation in CAVS. Additionally, we aim to draw parallels between other fibrotic disease and contributions to ECM post-translational modifications. Finally, we explore the current treatment options in pediatrics and identify how the field of proteomics has advanced in recent years, highlighting novel characterization methods of ECM and PTMs that may be used to identify potential therapeutic strategies relevant to pCAVS.

Automated summary

This article reviews the impact of extracellular matrix dysregulation on valve function in pediatric congenital aortic valve stenosis (pCAVS). It discusses the mechanisms of translational and post-translational dysregulation of ECM and explores contributing factors to this dysregulation. The article also draws parallels between ECM post-translational modifications in pCAVS and other fibrotic diseases. Additionally, it examines current treatment options in pediatrics and highlights the advancements in proteomics that may lead to potential therapeutic strategies for pCAVS.