Experimental animal models of coronary microvascular dysfunction

Autor: William M. Chilian, Daphne Merkus, Jens van de Wouw, Shawn B. Bender, Oana Sorop, Selena Chandler, Johnathan D. Tune, Vahagn Ohanyan, Dirk J. Duncker
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_specialty
Heart Diseases
Endothelium
Physiology
Cardiology
Ischemia
030204 cardiovascular system & hematology
Translational Research
Biomedical

Coronary artery disease
03 medical and health sciences
0302 clinical medicine
Coronary Circulation
Physiology (medical)
Diabetes mellitus
Internal medicine
medicine
Animals
Humans
Coronary microvascular dysfunction
Animal model
Endothelial dysfunction
Coronary atherosclerosis
Cause of death
business.industry
Microcirculation
Spotlight Review
INOCA
Metabolic derangements
medicine.disease
Coronary Vessels
Reactive Nitrogen Species
Comorbidity
3. Good health
Disease Models
Animal

Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Nitrosative Stress
Microvessels
Energy Metabolism
Reactive Oxygen Species
Cardiology and Cardiovascular Medicine
business
Zdroj: Cardiovascular Research
ISSN: 1755-3245
0008-6363
DOI: 10.1093/cvr/cvaa002
Popis: 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.
Databáze: OpenAIRE