Jürgen W. A. Sijbesma, Aren van Waarde, Sebastiaan Kristensen, Ilse Kion, Uwe J. F. Tietge, Jan-Luuk Hillebrands, Marian L. C. Bulthuis, Hendrik Buikema, Dalibor Nakladal, Marit Westerterp, Fan Liu, Hendrikus H. Boersma, Rudi A. J. O. Dierckx, Riemer H. J. A. Slart
{"title":"动脉粥样硬化成像新模型的特征:脂蛋白 E 缺乏大鼠","authors":"Jürgen W. A. Sijbesma, Aren van Waarde, Sebastiaan Kristensen, Ilse Kion, Uwe J. F. Tietge, Jan-Luuk Hillebrands, Marian L. C. Bulthuis, Hendrik Buikema, Dalibor Nakladal, Marit Westerterp, Fan Liu, Hendrikus H. Boersma, Rudi A. J. O. Dierckx, Riemer H. J. A. Slart","doi":"10.1186/s13550-023-01055-5","DOIUrl":null,"url":null,"abstract":"The apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE−/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE−/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging. ApoE−/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE−/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE−/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE−/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE−/− rats. These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE−/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat\",\"authors\":\"Jürgen W. A. Sijbesma, Aren van Waarde, Sebastiaan Kristensen, Ilse Kion, Uwe J. F. Tietge, Jan-Luuk Hillebrands, Marian L. C. Bulthuis, Hendrik Buikema, Dalibor Nakladal, Marit Westerterp, Fan Liu, Hendrikus H. Boersma, Rudi A. J. O. Dierckx, Riemer H. J. A. Slart\",\"doi\":\"10.1186/s13550-023-01055-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. 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Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat
The apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE−/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE−/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging. ApoE−/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE−/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE−/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE−/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE−/− rats. These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE−/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.
EJNMMI ResearchRADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍:
EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies.
The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.