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Role of animal models in HCM research
Rhian Shephard1, Christopher Semsarian
1Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Locked Bag 6, Newtown, Sydney, NSW, 2042, Australia.
Insights
Hypertrophic cardiomyopathy (HCM) is a genetic heart disorder. Animal models are crucial for understanding HCM mechanisms and developing new therapies to treat cardiac hypertrophy and heart failure.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Translational Medicine
Background:
- Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic cardiovascular disorder with significant unmet therapeutic needs.
- Current understanding of HCM pathogenesis remains incomplete, with no existing pharmacological treatments to prevent or reverse disease progression.
- Advances in clinical characterization and genetic mutation identification have been made, but mechanistic insights are still needed.
Purpose of the Study:
- To review key animal models of hypertrophic cardiomyopathy (HCM).
- To summarize how these models aid in understanding HCM disease mechanisms.
- To highlight the use of animal models in investigating novel therapeutic strategies for HCM.
Main Methods:
- Review of existing literature on hypertrophic cardiomyopathy (HCM) animal models.
- Analysis of how animal models have elucidated disease pathways, including cardiac hypertrophy, fibrosis, and heart failure.
- Examination of therapeutic approaches investigated in preclinical HCM studies using animal models.
Main Results:
- Animal models have been instrumental in confirming gene causation in HCM.
- These models have dissected molecular pathways underlying HCM development and its complications, such as heart failure and sudden death.
- Studies in animal models have guided the investigation of novel therapies targeting hypertrophy, fibrosis, and heart failure in HCM.
Conclusions:
- Animal models are essential tools for understanding hypertrophic cardiomyopathy (HCM) pathogenesis.
- Preclinical research using these models is vital for developing and testing new therapeutic interventions.
- Continued use of animal models promises to improve clinical outcomes for HCM patients through enhanced understanding and novel treatments.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a complex cardiovascular genetic disorder characterized by marked clinical and genetic heterogeneity. Major advances have been made in the clinical characterization of patients with HCM and in identifying causative gene mutations. However, many questions remain regarding the underlying disease mechanisms. Furthermore, in a disease where no pharmacological treatments currently exists which can either prevent or cause regression of disease, processes to identify novel therapies are the crucial next steps. Animal models of HCM have already proved to be universally useful in confirming gene causation and dissecting out key molecular pathways involved in the development of HCM and its sequelae, including heart failure and sudden death. These findings have led to studies in animal models investigating novel therapeutic approaches in HCM, specifically targeting the development and progression of cardiac hypertrophy, fibrosis, and heart failure. This review will provide a brief summary of some of the key animal models of HCM and how these models have been utilized to understand disease mechanisms and to investigate new potential therapies. Ongoing studies using animal models of HCM will lead to a greater understanding of disease pathogenesis and will facilitate the translation of these findings to improved clinical outcomes in HCM patients.
