Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Cardiovasc Res. 2020 Mar 1;116(4):756-770. doi: 10.1093/cvr/cvaa002.
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.
冠状动脉微血管功能障碍（CMD）在代谢紊乱患者中很常见，并且越来越被认为是心肌缺血的一个重要原因，无论是在有或没有心外膜冠状动脉粥样硬化的情况下。后者被称为“缺血但无阻塞性冠状动脉疾病（INOCA）”。尽管 INOCA 的患病率很高，但有效的治疗方法仍难以捉摸。尽管迄今为止还没有 INOCA 的动物模型，但 CMD 的动物模型，INOCA 的一个标志，为增强我们对 CMD 病理生理学的理解和研究新的治疗方法提供了极好的测试模型。本文概述了目前可用于 CMD 的实验模型——重点介绍了代谢紊乱作为危险因素——在狗、猪、兔、大鼠和小鼠中的应用。在所有现有的动物模型中，代谢紊乱最常通过高脂肪饮食（HFD）和/或通过注射链脲佐菌素或阿霉素诱导，糖尿病，但也有许多自发和转基因动物模型会发生代谢紊乱。根据危险因素的数量、严重程度和暴露时间——所有这些动物模型都显示出冠状动脉微血管（内皮）功能和结构的紊乱，类似于在 INOCA 患者和合并症患者中观察到的情况。这些动物模型的使用将有助于确定新的治疗靶点，并随后开发和测试新的治疗干预措施，以对抗全球头号死因缺血性心脏病。
