title: Imaging Reveals the Connection Between Spontaneous Coronary Plaque Ruptures, Atherothrombosis, and Myocardial Infarctions in HypoE/SRBI-/- Mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kuhlmann
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Starsichova
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Eligehausen
authors.affiliation: 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.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schäfers
authors.affiliation: Division of Cardiology, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Stypmann
authors.affiliation: Division of Cardiology, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Tiemann
authors.affiliation: Institute of Pathophysiology, University Duisburg-Essen, Essen, Germany; and.
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
mesh_terms: D000818:Animals; D003328:Coronary Thrombosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D012422:Rupture, Spontaneous / Q000000981:diagnostic imaging / Q000503:physiopathology
keywords: aspirin; atherosclerosis; hyperlipidemic mouse model; imaging; plaque vulnerability; thrombosis