Abstract | OBJECTIVE: METHODS:
ApoE-/- and LDLr-/- mice with or without (-/-) germline or bone marrow AMPKβ1, respectively, were treated with salsalate, and atherosclerotic plaque size was evaluated in serial sections of the aortic root. Studies examining the effects of salicylate on markers of inflammation, fatty acid and cholesterol synthesis and proliferation were conducted in bone marrow-derived macrophages (BMDMs) from wild-type mice or mice lacking AMPKβ1 or the key AMPK-inhibitory phosphorylation sites on ACC (ACC knock-in (KI)-ACC KI) or HMGCR (HMGCR-KI). RESULTS: CONCLUSIONS: These data indicate that salsalate suppresses macrophage proliferation and atherosclerosis through an AMPKβ1-dependent pathway, which may involve HMGCR phosphorylation and cholesterol synthesis. Since rapidly-proliferating macrophages are a hallmark of atherosclerosis, these data indicate further evaluation of salsalate as a potential therapeutic agent for treating atherosclerotic cardiovascular disease.
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Authors | Emily A Day, Rebecca J Ford, Brennan K Smith, Vanessa P Houde, Stephanie Stypa, Sonia Rehal, Sarka Lhotak, Bruce E Kemp, Bernardo L Trigatti, Geoff H Werstuck, Richard C Austin, Morgan D Fullerton, Gregory R Steinberg |
Journal | Molecular metabolism
(Mol Metab)
Vol. 53
Pg. 101321
(11 2021)
ISSN: 2212-8778 [Electronic] Germany |
PMID | 34425254
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved. |
Chemical References |
- Salicylates
- Prkab1 protein, mouse
- AMP-Activated Protein Kinases
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Topics |
- AMP-Activated Protein Kinases
(deficiency, metabolism)
- Animals
- Atherosclerosis
(metabolism)
- Cells, Cultured
- Mice
- Mice, Knockout
- Salicylates
(metabolism)
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