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

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

In: BASIC RES CARDIOL, Vol. 115, No. 6, 09.12.2020, p. 78.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Härdtner, C, Kornemann, J, Krebs, K, Ehlert, CA, Jander, A, Zou, J, Starz, C, Rauterberg, S, Sharipova, D, Dufner, B, Hoppe, N, Dederichs, T-S, Willecke, F, Stachon, P, Heidt, T, Wolf, D, von Zur Mühlen, C, Madl, J, Kohl, P, Kaeser, R, Boettler, T, Pieterman, EJ, Princen, HMG, Ho-Tin-Noé, B, Swirski, FK, Robbins, CS, Bode, C, Zirlik, A & Hilgendorf, I 2020, 'Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering', BASIC RES CARDIOL, vol. 115, no. 6, pp. 78. https://doi.org/10.1007/s00395-020-00838-4

APA

Härdtner, C., Kornemann, J., Krebs, K., Ehlert, C. A., Jander, A., Zou, J., Starz, C., Rauterberg, S., Sharipova, D., Dufner, B., Hoppe, N., Dederichs, T-S., Willecke, F., Stachon, P., Heidt, T., Wolf, D., von Zur Mühlen, C., Madl, J., Kohl, P., ... Hilgendorf, I. (2020). Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering. BASIC RES CARDIOL, 115(6), 78. https://doi.org/10.1007/s00395-020-00838-4

Vancouver

Härdtner C, Kornemann J, Krebs K, Ehlert CA, Jander A, Zou J et al. Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering. BASIC RES CARDIOL. 2020 Dec 9;115(6):78. https://doi.org/10.1007/s00395-020-00838-4

Bibtex

@article{2b2a467d93e440ffa133d129b6b89e56,
title = "Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering",
abstract = "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.",
author = "Carmen H{\"a}rdtner and Jan Kornemann and Katja Krebs and Ehlert, {Carolin A} and Alina Jander and Jiadai Zou and Christopher Starz and Simon Rauterberg and Diana Sharipova and Bianca Dufner and Natalie Hoppe and Tsai-Sang Dederichs and Florian Willecke and Peter Stachon and Timo Heidt and Dennis Wolf and {von Zur M{\"u}hlen}, Constantin and Josef Madl and Peter Kohl and Rafael Kaeser and Tobias Boettler and Pieterman, {Elsbeth J} and Princen, {Hans M G} and Beno{\^i}t Ho-Tin-No{\'e} and Swirski, {Filip K} and Robbins, {Clinton S} and Christoph Bode and Andreas Zirlik and Ingo Hilgendorf",
year = "2020",
month = dec,
day = "9",
doi = "10.1007/s00395-020-00838-4",
language = "English",
volume = "115",
pages = "78",
journal = "BASIC RES CARDIOL",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "6",

}

RIS

TY - JOUR

T1 - Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering

AU - Härdtner, Carmen

AU - Kornemann, Jan

AU - Krebs, Katja

AU - Ehlert, Carolin A

AU - Jander, Alina

AU - Zou, Jiadai

AU - Starz, Christopher

AU - Rauterberg, Simon

AU - Sharipova, Diana

AU - Dufner, Bianca

AU - Hoppe, Natalie

AU - Dederichs, Tsai-Sang

AU - Willecke, Florian

AU - Stachon, Peter

AU - Heidt, Timo

AU - Wolf, Dennis

AU - von Zur Mühlen, Constantin

AU - Madl, Josef

AU - Kohl, Peter

AU - Kaeser, Rafael

AU - Boettler, Tobias

AU - Pieterman, Elsbeth J

AU - Princen, Hans M G

AU - Ho-Tin-Noé, Benoît

AU - Swirski, Filip K

AU - Robbins, Clinton S

AU - Bode, Christoph

AU - Zirlik, Andreas

AU - Hilgendorf, Ingo

PY - 2020/12/9

Y1 - 2020/12/9

N2 - 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.

AB - 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.

U2 - 10.1007/s00395-020-00838-4

DO - 10.1007/s00395-020-00838-4

M3 - SCORING: Journal article

C2 - 33296022

VL - 115

SP - 78

JO - BASIC RES CARDIOL

JF - BASIC RES CARDIOL

SN - 0300-8428

IS - 6

ER -