Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering

  1. Härdtner, Carmen
  2. Kornemann, Jan
  3. Krebs, Katja
  4. Ehlert, Carolin A.
  5. Jander, Alina
  6. Zou, Jiadai
  7. Starz, Christopher
  8. Rauterberg, Simon
  9. Sharipova, Diana
  10. Dufner, Bianca
  11. Hoppe, Natalie
  12. Dederichs, Tsai-Sang
  13. Willecke, Florian
  14. Stachon, Peter
  15. Heidt, Timo
  16. Wolf, Dennis
  17. von zur Mühlen, Constantin
  18. Madl, Josef
  19. Kohl, Peter
  20. Kaeser, Rafael
  21. Boettler, Tobias
  22. Pieterman, Elsbeth J.
  23. Princen, Hans M. G.
  24. Ho-Tin-Noé, Benoît
  25. Swirski, Filip K.
  26. Robbins, Clinton S.
  27. Bode, Christoph
  28. Zirlik, Andreas
  29. Hilgendorf, Ingo ORCID logo

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1000 Titel
  • Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering
1000 Autor/in
  1. Härdtner, Carmen |
  2. Kornemann, Jan |
  3. Krebs, Katja |
  4. Ehlert, Carolin A. |
  5. Jander, Alina |
  6. Zou, Jiadai |
  7. Starz, Christopher |
  8. Rauterberg, Simon |
  9. Sharipova, Diana |
  10. Dufner, Bianca |
  11. Hoppe, Natalie |
  12. Dederichs, Tsai-Sang |
  13. Willecke, Florian |
  14. Stachon, Peter |
  15. Heidt, Timo |
  16. Wolf, Dennis |
  17. von zur Mühlen, Constantin |
  18. Madl, Josef |
  19. Kohl, Peter |
  20. Kaeser, Rafael |
  21. Boettler, Tobias |
  22. Pieterman, Elsbeth J. |
  23. Princen, Hans M. G. |
  24. Ho-Tin-Noé, Benoît |
  25. Swirski, Filip K. |
  26. Robbins, Clinton S. |
  27. Bode, Christoph |
  28. Zirlik, Andreas |
  29. Hilgendorf, Ingo |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-12-09
1000 Erschienen in
1000 Quellenangabe
  • 115(6):78
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00395-020-00838-4 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725697/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Mice, Inbred C57BL [MeSH]
lokal Original Contribution
lokal Macrophages/pathology [MeSH]
lokal Atherosclerosis
lokal Macrophages/metabolism [MeSH]
lokal Atherosclerosis/pathology [MeSH]
lokal Atorvastatin/pharmacology [MeSH]
lokal Plaque regression
lokal Atherosclerosis/therapy [MeSH]
lokal Atherosclerosis/metabolism [MeSH]
lokal Disease Models, Animal [MeSH]
lokal Female [MeSH]
lokal Down-Regulation [MeSH]
lokal Macrophages/drug effects [MeSH]
lokal Apolipoprotein E3/genetics [MeSH]
lokal Biomarkers/blood [MeSH]
lokal Humans [MeSH]
lokal Diet, Fat-Restricted [MeSH]
lokal Macrophage
lokal Animals [MeSH]
lokal Cholesterol Ester Transfer Proteins/genetics [MeSH]
lokal Mice, Knockout, ApoE [MeSH]
lokal Atherosclerosis/genetics [MeSH]
lokal Plaque, Atherosclerotic [MeSH]
lokal Proliferation
lokal Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology [MeSH]
lokal Cholesterol, LDL/blood [MeSH]
lokal Cell Proliferation/drug effects [MeSH]
lokal Receptors, LDL/genetics [MeSH]
1000 Liste der Beteiligten
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1000 Erstellt am 2023-11-16T23:11:22.577+0100
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