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Author Sitaula, Sadichha ♦ Billon, Cyrielle ♦ Kamenecka, Theodore M. ♦ Solt, Laura A. ♦ Burris, Thomas P.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ARTERIOSCLEROSIS ♦ BONE MARROW ♦ COMPARATIVE EVALUATIONS ♦ CONTROL ♦ HEME ♦ INFLAMMATION ♦ INHIBITION ♦ MACROPHAGES ♦ METABOLISM ♦ MICE ♦ POLARIZATION ♦ RECEPTORS
Abstract The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-05-08
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 460
Issue Number 3


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