Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, CA, USA.
Pflugers Arch. 2019 May;471(5):745-753. doi: 10.1007/s00424-018-2209-x. Epub 2018 Oct 3.
Comparative and translation medicine is of particular value within the field of inherited cardiomyopathies. Despite massive advances in understanding the functional role of mutations in human cardiomyopathies, these advances have frequently failed to translate into medical discoveries that alter patient care. One potential explanation for this failure lies in the lack of suitable translational models that adequately recapitulate human cardiovascular physiology and disease expression. The vast genetic heterogeneity that complicates human cardiomyopathy research is potentially alleviated through the study of naturally occurring large animal models of disease, where incredibly homogenous populations, like those seen in a single breed of dog or cat, may exist (Kol et al., Sci Transl Med 7:308-321, 2015; Ueda and Stern, Yale J Biol Med 90:433-448, 2017). Veterinary medicine is in a unique position to provide research resources and information that may be readily applied to human disease (Kol et al., Sci Transl Med 7:308-321, 2015). Many inherited cardiomyopathies of humans are phenotypically and genotypically similar in veterinary species and ongoing research holds promise for aiding veterinary and human patients alike (Basso et al., Circulation 109:1180-1185, 2004; Fox et al., Cardiovasc Pathol 23:28-34, 2014; Fox et al., Circulation 102:1863-1870, 2000; Kittleson et al., J Vet Cardiol 17 Suppl 1:S53-73, 2015; Ueda and Stern, Yale J Biol Med 90:433-448, 2017). This article presents the current knowledge of inherited cardiomyopathies in dogs, cats, and non-human primates, with a goal of identifying areas of translational research and future directions.
比较医学和转化医学在遗传性心肌病领域具有特别的价值。尽管在理解人类心肌病突变的功能作用方面取得了巨大进展,但这些进展常常未能转化为改变患者治疗的医学发现。这种失败的一个潜在解释是缺乏充分再现人类心血管生理学和疾病表现的合适转化模型。通过研究自然发生的大型动物疾病模型,可以缓解人类心肌病研究中巨大的遗传异质性问题,在这些模型中,可能存在着非常同质的群体,就像在单一品种的狗或猫中看到的那样(Kol 等人,《科学转化医学》7:308-321,2015 年;Ueda 和 Stern,《耶鲁大学生物医学杂志》90:433-448,2017 年)。兽医医学处于提供可轻易应用于人类疾病的研究资源和信息的独特地位(Kol 等人,《科学转化医学》7:308-321,2015 年)。许多人类遗传性心肌病在兽医物种中表型和基因型相似,正在进行的研究有望为兽医和人类患者提供帮助(Basso 等人,《循环》109:1180-1185,2004 年;Fox 等人,《心血管病理学》23:28-34,2014 年;Fox 等人,《循环》102:1863-1870,2000 年;Kittleson 等人,《兽医心脏病学杂志》17 增刊 1:S53-73,2015 年;Ueda 和 Stern,《耶鲁大学生物医学杂志》90:433-448,2017 年)。本文介绍了犬、猫和非人类灵长类动物遗传性心肌病的现有知识,旨在确定转化研究的领域和未来的方向。