Pressure overload leads to coronary plaque formation, progression, and myocardial events in ApoE–/– mice
Alice Marino, Yi Zhang, Luisa Rubinelli, Maria Antonietta Riemma, James E. Ip, Annarita Di Lorenzo
Alice Marino, Yi Zhang, Luisa Rubinelli, Maria Antonietta Riemma, James E. Ip, Annarita Di Lorenzo
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Research Article Cardiology Vascular biology

Pressure overload leads to coronary plaque formation, progression, and myocardial events in ApoE–/– mice

Abstract

Hypercholesterolemia and hypertension are two major risk factors for coronary artery diseases, which remain the major cause of mortality in the industrialized world. Current animal models of atherosclerosis do not recapitulate coronary plaque disruption, thrombosis, and myocardial infarction occurring in humans. Recently, we demonstrated that exposure of the heart to high pressure, by transverse aortic constriction (TAC), induced coronary lesions in ApoE–/– mice on chow diet. The aim of this study was to characterize the magnitude and location of coronary lesions in ApoE–/– mice after TAC and to assess the susceptibility of coronary plaque to disruption, leading to myocardial events. Here, we describe a reliable pathological condition in mice characterized by the development of coronary lesions and its progression, leading to myocardial infarction; this model better recapitulates human disease. Following TAC surgery, about 90% of ApoE–/– mice developed coronary lesions, especially in the left anterior descending artery, with 59% of the mice manifesting a different magnitude of LAD stenosis. Myocardial events, identified in 74% of the mice, were mainly due to coronary plaque thrombosis and occlusion. That TAC-induced development and progression of coronary lesions in ApoE–/– mice, leading to myocardial events, represents a potentially novel and important tool to investigate the development of coronary lesions and its sequelae in a setting that better resemble human conditions.

Authors

Alice Marino, Yi Zhang, Luisa Rubinelli, Maria Antonietta Riemma, James E. Ip, Annarita Di Lorenzo

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Figure 7

Causes of MI in TAC-operated ApoE–/– mice subjected to physical stress.

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Causes of MI in TAC-operated ApoE–/– mice subjected to physical stress. ...
(A) Pie diagram of the TAC-operated ApoE–/– mice that died during the physical stress protocol: 74% of the mice presented evidence of MI, determined by TTC staining or ECG and histological analysis; 9% did not show evidence of coronary plaque and MI; and 17% of the mice were discarded by the technicians of the Research Animal Resource Center and therefore the heart were not collected (n = 23 TAC-operated ApoE–/– mice). (B) Pie diagram illustrating the causes of MI of the 74% of animals that died during physical stress: 40% of the mice showed coronary occlusion; 34% had evidence of plaque rupture; 13% had evidence of plaque erosion; and 13% had evidence coronary embolism (n = 15 TAC-operated ApoE–/– mice).