Details

Autor(en) / Beteiligte

• Sitaula, Sadichha
• Billon, Cyrielle
• Kamenecka, Theodore M.
• Solt, Laura A.
• Burris, Thomas P.

Titel

Suppression of atherosclerosis by synthetic REV-ERB agonist

Ist Teil von

• Biochemical and biophysical research communications, 2015-05, Vol.460 (3), p.566-571

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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. •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.