Abstract
Background: The hyperlipidemic mouse model HypoE/SRBI-/- has been shown to develop occlusive coronary atherosclerosis followed by myocardial infarctions and premature deaths in response to high-fat, high-cholesterol diet (HFC). However, the causal connection between myocardial infarctions and atherosclerotic plaque rupture events in the coronary arteries has not been investigated so far. Objective: To assess whether diet-induced coronary plaque ruptures trigger atherothrombotic occlusions resulting in myocardial infarctions in HFC-fed HypoE/SRBI-/- mice. Methods: HypoE/SRBI-/- mice were characterized with respect to the individual dynamics of myocardial infarction(s) and features of infarct-related coronary atherosclerosis by serial non-invasive molecular and functional imaging, histopathology, and a pharmaceutical intervention. Detailed histological analysis of whole mouse hearts was performed when spontaneously occurring acute myocardial infarctions were diagnosed by imaging. Results: Using the imaging-triggered approach we discovered thrombi in 32 (10.8%) of all 296 atherosclerotic coronary plaques in 14 HFC-fed HypoE/SRBI-/- mice. These thrombi typically were found in arteries presenting with inflammatory plaque phenotypes. Acetylsalicylic acid treatment did not attenuate the development of atherosclerotic coronary plaques, but profoundly reduced the incidence of premature deaths, the number of thrombi (7 in 249 plaques) and also the degree of inflammation in the culprit lesions. Conclusions: HFC-induced ruptures of coronary plaques trigger atherothrombosis, vessel occlusions, myocardial infarctions and sudden death in HypoE/SRBI-/- mice. Thus, the HypoE/SRBI-/- mouse model mimics major features of human coronary heart disease and might therefore be a valuable model for the investigation of molecular and cellular parameters driving plaque rupture-related events and the development of new interventional approaches.
- Animal Imaging
- Cardiology (basic/technical)
- Vascular
- atherosclerosis
- hyperlipidemic mouse model
- imaging
- plaque vulnerability
- thrombosis
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.