Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Härdtner, C; Kornemann, J; Krebs, K; Ehlert, CA; Jander, A; Zou, J; Starz, C; Rauterberg, S; Sharipova, D; Dufner, B; Hoppe, N; Dederichs, TS; 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.
Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering.
Basic Res Cardiol. 2020; 115(6): 78-78. Doi: 10.1007/s00395-020-00838-4 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Zirlik Andreas
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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.
Find related publications in this database (Keywords): Atherosclerosis; Macrophage; Proliferation; Plaque regression