期刊
CARDIOVASCULAR RESEARCH
卷 116, 期 4, 页码 756-770出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvaa002
关键词
Coronary microvascular dysfunction; Animal model; Metabolic derangements; Endothelial dysfunction; INOCA
资金
- European Commission FP7-Health-2010 [MEDIA-261409]
- Netherlands Cardiovascular Research Initiative [CVON2014-11]
- Dutch Heart Foundation
- DZHK (German Centre for Cardiovascular Research) [81Z0600207]
- National Institutes of Health [R01 HL136386, HL118738, HL135024, HL135110]
Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischaemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed `ischaemia and no obstructive coronary artery disease' (INOCA). Notwithstanding the high prevalence of INOCA, effective treatment remains elusive. Although to date there is no animal model for INOCA, animal models of CMD, one of the hallmarks of INOCA, offer excellent test models for enhancing our understanding of the pathophysiology of CMD and for investigating novel therapies. This article presents an overview of currently available experimental models of CMD-with an emphasis on metabolic derangements as risk factors-in dogs, swine, rabbits, rats, and mice. In all available animal models, metabolic derangements are most often induced by a high-fat diet (HFD) and/or diabetes mellitus via injection of alloxan or streptozotocin, but there is also a wide variety of spontaneous as well as transgenic animal models which develop metabolic derangements. Depending on the number, severity, and duration of exposure to risk factors-all these animal models show perturbations in coronary microvascular (endothelial) function and structure, similar to what has been observed in patients with INOCA and comorbid conditions. The use of these animal models will be instrumental in identifying novel therapeutic targets and for the subsequent development and testing of novel therapeutic interventions to combat ischaemic heart disease, the number one cause of death worldwide.
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