Experimental animal models of coronary microvascular dysfunction.

Experimental animal models of coronary microvascular dysfunction.

Sorop Oana; van de Wouw Jens; Chandler Selena; Ohanyan Vahagn; Tune Johnathan D; Chilian William M; Merkus Daphne; Bender Shawn B; Duncker Dirk J

Cardiovascular research

2020

2020-01

Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed 'ischemia with non-obstructive coronary arteries' (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 the available animal models, metabolic derangements are most often induced by a high fat diet 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 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 co-morbid 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 ischemic heart disease, the number one cause of death worldwide.

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Journal Article

NEOMED College of Medicine

NEOMED Student Publications; Department of Integrative Medical Sciences

March 2020 Update