Premium
Atorvastatin inhibits induction of chemokine receptor CXCR7 to reduce macrophage migration (1148.12)
Author(s) -
Liu Yiwei,
Ma Wanshu,
Crocker Laura,
Shen Jianzhong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1148.12
Subject(s) - atorvastatin , pharmacology , chemistry , geranylgeranylation , macrophage , abcg1 , prenylation , biology , biochemistry , enzyme , in vitro , transporter , gene , abca1
We recently reported that the new SDF‐1 receptor CXCR7 is induced during monocyte‐to‐macrophage differentiation in the context of atherosclerosis. This study aimed to determine whether CXCR7 induction during macrophage differentiation is inhibited by statins. Here we show that atorvastatin inhibited CXCR7 mRNA and protein expression in THP‐1 macrophages, without affecting CXCR4 expression. Suppression of CXCR7 expression was reversed by supplementation with mevalonate. Inhibition of squalene synthase, the enzyme committed to cholesterol biosynthesis, partially decreased CXCR7 induction. However, the geranylgeranyl transferase inhibitor, GGTI‐286, the farnesyl transferase inhibitor, FTI‐276, and the Rho kinase inhibitor, Y‐27632, all failed to mimic the effect of atorvastatin, suggesting that the protein prenylation pathways are not critical. Interestingly, the effect of atorvastatin was not fully mimicked by other statins. Furthermore, activation of CXCR7 by SDF‐1, TC14012, or I‐TAC all prompted macrophage migration, which was suppressed by atorvastatin treatment, but not by the CXCR4 antagonist. We conclude that atorvastatin modulates macrophage migration by down‐regulating CXCR7 expression, suggesting a new CXCR7‐dependent mechanism of atorvastatin to benefit atherosclerosis treatment independent of its lipid lowering effect. Grant Funding Source : American Heart Association ─ National SDG grant 12SDG8850011