title: Large animal models of cardiovascular disease.
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.
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
authors.forename: H G
authors.initials: HG
authors.lastname: Tsang
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Rashdan
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
authors.forename: C B A
authors.initials: CB
authors.lastname: Whitelaw
authors.affiliation: Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Corcoran
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Summers
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.
authors.forename: V E
authors.initials: VE
authors.lastname: MacRae
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans
keywords: Marfan syndrome; aortic stenosis; calcific aortic valve disease; cardiovascular disease; genetic engineering; large animal models; vascular calcification