دورية أكاديمية
Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering
| العنوان: | Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering |
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| المؤلفون: | Härdtner, Carmen, Kornemann, Jan, Krebs, Katja, Ehlert, Carolin A., Jander, Alina, Zou, Jiadai, Starz, Christopher, Rauterberg, Simon, Sharipova, Diana, Dufner, Bianca, Hoppe, Natalie, Dederichs, Tsai-Sang, Willecke, Florian, Stachon, Peter, Heidt, Timo, Wolf, Dennis, von zur Mühlen, Constantin, Madl, Josef, Kohl, Peter, Kaeser, Rafael, Boettler, Tobias, Pieterman, Elsbeth J., Princen, Hans M. G., Ho-Tin-Noé, Benoît, Swirski, Filip K., Robbins, Clinton S., Bode, Christoph, Zirlik, Andreas, Hilgendorf, Ingo |
| المصدر: | http://lobid.org/resources/99370671625606441Test#!, 115(6):78. |
| سنة النشر: | 2020 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Mice, Inbred C57BL [MeSH], Original Contribution, Macrophages/pathology [MeSH], Atherosclerosis, Macrophages/metabolism [MeSH], Atherosclerosis/pathology [MeSH], Atorvastatin/pharmacology [MeSH], Plaque regression, Atherosclerosis/therapy [MeSH], Atherosclerosis/metabolism [MeSH], Disease Models, Animal [MeSH], Female [MeSH], Down-Regulation [MeSH], Macrophages/drug effects [MeSH], Apolipoprotein E3/genetics [MeSH], Biomarkers/blood [MeSH], Humans [MeSH], Diet, Fat-Restricted [MeSH], Macrophage, Animals [MeSH], Cholesterol Ester Transfer Proteins/genetics [MeSH], Knockout, ApoE [MeSH], Atherosclerosis/genetics [MeSH], Plaque, Atherosclerotic [MeSH], Proliferation |
| الوصف: | Statins induce plaque regression characterized by reduced macrophage content in humans, but the underlying mechanisms remain speculative. Studying the translational APOE*3-Leiden.CETP mouse model with a humanized lipoprotein metabolism, we find that systemic cholesterol lowering by oral atorvastatin or dietary restriction inhibits monocyte infiltration, and reverses macrophage accumulation in atherosclerotic plaques. Contrary to current believes, none of (1) reduced monocyte influx (studied by cell fate mapping in thorax-shielded irradiation bone marrow chimeras), (2) enhanced macrophage egress (studied by fluorescent bead labeling and transfer), or (3) atorvastatin accumulation in murine or human plaque (assessed by mass spectrometry) could adequately account for the observed loss in macrophage content in plaques that undergo phenotypic regression. Instead, suppression of local proliferation of macrophages dominates phenotypic plaque regression in response to cholesterol lowering: the lower the levels of serum LDL-cholesterol and lipid contents in murine aortic and human carotid artery plaques, the lower the rates of in situ macrophage proliferation. Our study identifies macrophage proliferation as the predominant turnover determinant and an attractive target for inducing plaque regression. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| ردمك: | 978-9937-0-6716-4 9937-0-6716-2 |
| العلاقة: | https://repository.publisso.de/resource/frl:6466430Test; https://doi.org/10.1007/s00395-020-00838-4Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725697Test/ |
| DOI: | 10.1007/s00395-020-00838-4 |
| الإتاحة: | https://doi.org/10.1007/s00395-020-00838-4Test https://repository.publisso.de/resource/frl:6466430Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725697Test/ |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.3DCEB482 |
| قاعدة البيانات: | BASE |
| ردمك: | 9789937067164 9937067162 |
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| DOI: | 10.1007/s00395-020-00838-4 |