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Collagen fiber regulation in human pediatric aortic valve development and disease

Cassandra L Clift1, Yan Ru Su2, David Bichell3

  • 1Department of Cell and Molecular Pharmacology, MUSC Proteomics Center, Bruker-MUSC Clinical Glycomics Center of Excellence, Medical University of South Carolina, 173 Ashley Ave, BSB358, Charleston, SC, 29425, USA.

Scientific Reports
|May 8, 2021
PubMed

Insights

This study reveals collagen changes in congenital aortic valve stenosis (CAVS), identifying hydroxylated prolines (HYP) as key regulators. Findings offer new targets to prevent valvular degradation in pediatric CAVS (pCAVS).

Area of Science:

  • Biochemistry
  • Cardiovascular Biology
  • Developmental Biology

Background:

  • Congenital aortic valve stenosis (CAVS) impacts global health, lacking effective medical treatments.
  • Collagen deregulation is a known feature of CAVS but remains poorly understood.
  • Identifying molecular targets is crucial for halting CAVS progression.

Purpose of the Study:

  • To investigate collagen fiber production and regulation during human aortic valve (AV) development and in pediatric end-stage CAVS (pCAVS).
  • To identify specific collagen types and post-translational modifications involved in CAVS.
  • To explore potential upstream regulators of collagen remodeling in the context of CAVS.

Main Methods:

  • Histological analysis of human AV tissues to examine collagen fiber structure.
  • High-resolution accurate mass (HRAM) proteomics targeting collagen.
  • Quantitative analysis of collagen peptides and post-translational modifications, including hydroxylated prolines (HYP).
  • Bioinformatic network analysis to identify regulatory interactions.

Main Results:

  • Histology revealed collagen fiber realignment and high-density regions in pCAVS.
  • Proteomics identified specific collagen peptides with hydroxylated proline (HYP) modifications.
  • Significant regulation of collagen HYP sites was observed across patient groups.
  • Non-collagen extracellular matrix (ECM) proteins interacting with collagen were identified.
  • BAMBI (BMP and Activin Membrane Bound Inhibitor) emerged as a potential regulator of the collagen interactome.

Conclusions:

  • This study provides the first detailed characterization of collagen types and HYP modifications in human AV development and pCAVS.
  • The findings highlight the critical role of collagen remodeling and HYP in CAVS.
  • This research may lead to novel therapeutic strategies targeting valvular degradation in pCAVS and inform valve replacement engineering.

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