Publications by authors named "Diana Sharipova"

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

Basic Res Cardiol 2020 12 9;115(6):78. Epub 2020 Dec 9.

Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen and Faculty of Medicine, University of Freiburg, 55 Hugstetter St, 79106, Freiburg, Germany.

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.
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http://dx.doi.org/10.1007/s00395-020-00838-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725697PMC
December 2020
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