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Published on: October 9, 2017
Large animal models of cardiovascular disease
H G Tsang1, N A Rashdan1, C B A Whitelaw1
1The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
Insights
Large animal models offer superior human similarity for studying cardiovascular disease (CVD) mechanisms. Advanced genome editing in these models accelerates translational research and therapeutic development for CVD.
Area of Science:
- Cardiovascular Science
- Translational Medicine
- Genomics
Background:
- Cardiovascular disease (CVD) remains a global health challenge, with increasing incidence in aging populations.
- Rodent models have limitations due to significant physiological and pathological differences from humans.
- Understanding the molecular landscape (genome, transcriptome, proteome) is key to unraveling CVD complexity.
Purpose of the Study:
- To highlight the limitations of current rodent models in cardiovascular research.
- To emphasize the potential of large animal models for studying human cardiovascular disease.
- To explore the role of genome editing in creating advanced models for translational research.
Main Methods:
- Comparative analysis of cardiovascular systems across species.
- Review of advancements in genome editing technologies.
- Discussion of large animal models for in vivo cardiovascular research.
Main Results:
- Large animal models exhibit greater anatomical, physiological, and pathological similarity to humans compared to rodents.
- Genome editing enables the creation of precise, tailored large animal models.
- These models facilitate in vivo investigation of CVD regulatory factors and molecular pathways.
Conclusions:
- Large animal models, enhanced by genome editing, are crucial for bridging basic science and clinical applications in CVD.
- These advanced models hold significant potential for refining existing and developing novel cardiovascular therapies.
- Further utilization of these models can improve our understanding and treatment of cardiovascular diseases.
Abstract:
The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone-formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease.
