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Updated: Jan 10, 2026

Isolation of Human Primary Valve Cells for In vitro Disease Modeling
Published on: April 16, 2021
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.
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.
Abstract:
Calcific aortic valve disease (CAVD) is characterized by a fibrocalcific remodeling of the aortic valve. This pathology is the most prevalent valvular heart disease worldwide and is associated with a poor prognosis. Despite extensive research, no pharmacological treatments are available to slow or reverse valvular degeneration, making aortic valve replacement the only current therapeutic option. This lack of clinical success may stem from an incomplete understanding of the disease's mechanisms and the limitations of current preclinical models, which do not fully replicate the complexity of CAVD and its associated risk factors and comorbidities. Indeed, while existing models offer valuable insights, a deeper understanding of CAVD requires incorporating comorbidities, gender-specific mechanisms, and dynamic cellular and tissue-level changes. This review aims to provide the reader with an overview of preclinical models developed in recent years to study CAVD, assessing their strengths and limitations. We review how these models can be used to mimic and/or investigate the cellular and molecular mechanisms involved in CAVD development, and highlight how key risk factors and comorbidities can be incorporated to enhance the translational potential of research. We hope that this approach will help guide researchers in selecting the most appropriate model for their studies, with the goal of advancing the identification of effective therapeutic candidates.

