Insights into preclinical models of calcific aortic valve disease and their translational potential

Isabelle Lafosse1, Romuald Mentaverri1,2, Carine Avondo1

  • 1UR UPJV 7517 MP3CV, CURS, Amiens, France.

PubMed

Insights

Calcific aortic valve disease (CAVD) lacks effective treatments due to incomplete understanding and limited preclinical models. This review assesses current models for studying CAVD mechanisms, risk factors, and comorbidities to advance therapeutic development.

Area of Science:

  • Cardiovascular Research
  • Translational Medicine
  • Biomedical Engineering

Background:

  • Calcific aortic valve disease (CAVD) is the most common valvular heart disease globally, characterized by aortic valve degeneration and a poor prognosis.
  • Current therapeutic options for CAVD are limited to surgical or transcatheter aortic valve replacement, as no pharmacological treatments exist to halt or reverse disease progression.
  • Existing preclinical models often fail to fully replicate the complex interplay of risk factors, comorbidities, and dynamic cellular changes inherent to human CAVD, hindering therapeutic development.

Purpose of the Study:

  • To provide a comprehensive overview of recent preclinical models for studying CAVD.
  • To assess the strengths and limitations of various models in mimicking CAVD development and progression.
  • To guide researchers in selecting appropriate models for investigating CAVD mechanisms and identifying therapeutic targets.

Main Methods:

  • Systematic review of preclinical models used in recent years for CAVD research.
  • Analysis of how models incorporate key CAVD risk factors and comorbidities.
  • Evaluation of models' utility in studying cellular and molecular mechanisms of valvular degeneration.

Main Results:

  • Preclinical models vary in their ability to replicate CAVD complexity, including cellular dynamics and risk factor integration.
  • Incorporating comorbidities and gender-specific factors into models enhances their translational relevance.
  • Models offer insights into molecular pathways but require further refinement to fully capture disease heterogeneity.

Conclusions:

  • Improved preclinical models are crucial for advancing the understanding of CAVD pathogenesis.
  • Selecting appropriate models that incorporate disease complexity is essential for successful drug discovery.
  • Further development of translational models will accelerate the identification of effective pharmacological treatments for CAVD.

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