Sven Hermann1, Michael T Kuhlmann2, Andrea Starsichova2, Sarah Eligehausen2, Klaus Schäfers3, Jörg Stypmann4, Klaus Tiemann4, Bodo Levkau5, Michael Schäfers6. 1. European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany DFG EXC 1003 Cluster of Excellence 'Cells in Motion', University of Münster, Münster, Germany shermann@uni-muenster.de. 2. European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany. 3. European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany DFG EXC 1003 Cluster of Excellence 'Cells in Motion', University of Münster, Münster, Germany. 4. Division of Cardiology, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany. 5. Institute of Pathophysiology, University Duisburg-Essen, Essen, Germany; and. 6. European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany DFG EXC 1003 Cluster of Excellence 'Cells in Motion', University of Münster, Münster, Germany Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
Abstract
UNLABELLED: 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. The objective of this study was 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 infarctions and features of infarct-related coronary atherosclerosis by serial noninvasive molecular and functional imaging, histopathology, and a pharmaceutical intervention. Detailed histologic 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. CONCLUSION: HFC-induced ruptures of coronary plaques trigger atherothrombosis, vessel occlusions, myocardial infarctions, and sudden death in these 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.
UNLABELLED: 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. The objective of this study was 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 infarctions and features of infarct-related coronary atherosclerosis by serial noninvasive molecular and functional imaging, histopathology, and a pharmaceutical intervention. Detailed histologic 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. CONCLUSION: HFC-induced ruptures of coronary plaques trigger atherothrombosis, vessel occlusions, myocardial infarctions, and sudden death in these mice. Thus, the HypoE/SRBI(-/-) mouse model mimics major features of humancoronary 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.
Authors: Stefan Hof; Carsten Marcus; Anne Kuebart; Jan Schulz; Richard Truse; Annika Raupach; Inge Bauer; Ulrich Flögel; Olaf Picker; Anna Herminghaus; Sebastian Temme Journal: Front Med (Lausanne) Date: 2022-05-16
Authors: Paula R Pinto; Karolline S da Silva; Rodrigo T Iborra; Ligia S Okuda; Diego Gomes-Kjerulf; Guilherme S Ferreira; Adriana Machado-Lima; Debora D F M Rocco; Edna R Nakandakare; Ubiratan F Machado; Maria L Correa-Giannella; Sergio Catanozi; Marisa Passarelli Journal: Front Physiol Date: 2018-05-08 Impact factor: 4.566