Mouse models of atherosclerosis and their suitability for the study of myocardial infarction
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REVIEW
Mouse models of atherosclerosis and their suitability for the study of myocardial infarction Pelin Golforoush1 · Derek M. Yellon1 · Sean M. Davidson1 Received: 31 July 2020 / Accepted: 28 October 2020 © The Author(s) 2020
Abstract Atherosclerotic plaques impair vascular function and can lead to arterial obstruction and tissue ischaemia. Rupture of an atherosclerotic plaque within a coronary artery can result in an acute myocardial infarction, which is responsible for significant morbidity and mortality worldwide. Prompt reperfusion can salvage some of the ischaemic territory, but ischaemia and reperfusion (IR) still causes substantial injury and is, therefore, a therapeutic target for further infarct limitation. Numerous cardioprotective strategies have been identified that can limit IR injury in animal models, but none have yet been translated effectively to patients. This disconnect prompts an urgent re-examination of the experimental models used to study IR. Since coronary atherosclerosis is the most prevalent morbidity in this patient population, and impairs coronary vessel function, it is potentially a major confounder in cardioprotective studies. Surprisingly, most studies suggest that atherosclerosis does not have a major impact on cardioprotection in mouse models. However, a major limitation of atherosclerotic animal models is that the plaques usually manifest in the aorta and proximal great vessels, and rarely in the coronary vessels. In this review, we examine the commonly used mouse models of atherosclerosis and their effect on coronary artery function and infarct size. We conclude that none of the commonly used strains of mice are ideal for this purpose; however, more recently developed mouse models of atherosclerosis fulfil the requirement for coronary artery lesions, plaque rupture and lipoprotein patterns resembling the human profile, and may enable the identification of therapeutic interventions more applicable in the clinical setting. Keywords Atherosclerosis · Ischaemia · Reperfusion · Cardioprotection · Myocardial infarction · Mice · Coronary artery · Vascular function
Introduction Myocardial infarction and protection from ischaemia/reperfusion injury Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for an estimated 17.9 million deaths annually, representing 31% of all global deaths [149]. Four out of five CVD associated deaths are caused by myocardial infarction (MI) and ischaemic stroke [149]. These figures show there is an immediate need for appropriate interventions to improve survival and prognosis for CVD patients. * Sean M. Davidson [email protected] 1
The Hatter Cardiovascular Institute, 67 Chenies Mews, London WC1E 6HX, UK
MI is caused by obstruction of blood flow through one of the major coronary arteries supplying the myocardium, usually due to atherosclerotic plaque rupture and thrombosis. Prolonged ischaemia results in oncotic, necrotic, apoptotic and necroptotic death of heart muscle [31, 45, 96, 103]. The extent of cell death
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