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.

中文翻译：

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冠状动脉微血管功能障碍的实验动物模型。

冠状动脉微血管功能障碍（CMD）通常存在于代谢紊乱的患者中，并且越来越多地被认为是心肌缺血的重要原因，无论是否存在心外膜冠状动脉粥样硬化。后一种情况被称为“缺血且无阻塞性冠状动脉疾病”(INOCA)。尽管 INOCA 患病率很高，但有效的治疗方法仍然难以实现。尽管迄今为止还没有 INOCA 的动物模型，但 INOCA 的标志之一 CMD 动物模型为增强我们对 CMD 病理生理学的理解和研究新疗法提供了极好的测试模型。本文概述了目前可用的 CMD 实验模型，重点关注狗、猪、兔子、大鼠和小鼠的代谢紊乱作为危险因素。在所有可用的动物模型中，代谢紊乱最常是由高脂饮食（HFD）和/或糖尿病通过注射四氧嘧啶或链脲佐菌素引起的，但也有多种自发的和转基因的动物模型代谢紊乱。根据暴露于危险因素的数量、严重程度和持续时间，所有这些动物模型都表现出冠状动脉微血管（内皮）功能和结构的扰动，类似于在 INOCA 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，并有助于随后开发和测试新的治疗干预措施，以对抗缺血性心脏病（全球第一大死亡原因）。