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Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation.

Christine B Kern1

  • 1Department of Regenerative Medicine and Cell Biology, 171 Ashley Avenue, Medical University of South Carolina, Charleston, SC 29425, USA.

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|August 26, 2021
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Summary

Excess versican in the provisional extracellular matrix is a common factor in bicuspid aortic valve (BAV) development across mouse models. This finding may lead to new BAV therapeutics and biomarkers for this prevalent heart defect.

Keywords:
NOTCH1aortaaortic valvebicuspid aortic valveneural crestoutflow tractversican

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Area of Science:

  • Cardiovascular Research
  • Developmental Biology
  • Genetics

Background:

  • Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 0.5-2% of the population.
  • BAV is linked to severe aortic stenosis and aortic aneurysms, with no current targeted therapeutics.
  • Genetically modified mouse models are crucial for understanding BAV's molecular underpinnings.

Purpose of the Study:

  • To investigate common molecular pathways in BAV development by comparing phenotypic characteristics across different murine models.
  • To identify shared molecular features that could reveal therapeutic targets and biomarkers for BAV.

Main Methods:

  • Comparative analysis of phenotypic characteristics in various genetically modified murine models of BAV.
  • Collation and analysis of data on extracellular matrix composition, specifically versican levels.

Main Results:

  • Excess versican within the provisional extracellular matrix (P-ECM) was identified as a common factor in BAV development across multiple murine models.
  • Mutant mice, even those with low BAV incidence, showed altered tricuspid aortic valves with excess P-ECM compared to controls.

Conclusions:

  • Common molecular characteristics, particularly excess versican in the P-ECM, are associated with BAV formation in mice.
  • These findings suggest potential therapeutic targets and biomarkers for BAV, a prevalent and heterogeneous cardiovascular malformation.