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IRS-2 deficiency in macrophages promotes their accumulation in the vascular wall

  作者 Mita, T; Azuma, K; Goto, H; Jin, WL; Arakawa, M; Nomiyama, T; Suzuki, R; Kubota, N; Tobe, K; Kadowaki, T; Fujitani, Y; Hirose, T; Kawamori, R; Watada, H  
  选自 期刊  Biochemical and Biophysical Research Communications;  卷期  2011年415-4;  页码  545-550  
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[摘要]The aim of this study was to investigate the role of insulin receptor substrate-2 (IRS-2) mediated signal in macrophages on the accumulation of macrophages in the vascular wall. Mice transplanted with IRS-2(-/-) bone marrow, a model of myeloid cell restricted defect of IRS-2, showed accumulation of monocyte chemoattractant protein-1-expressing macrophages in the vascular wall. Experiments using cultured peritoneal macrophages showed that IRS-2-mediated signal pathway stimulated by physiological concentrations of insulin, not by IL-4, contributed to the suppression of monocyte chemoattractant protein-1 expression induced by lipopolysaccharide. Our data indicated that IRS-2 deficiency in macrophages enhanced their accumulation in the vascular wall accompanied by increased expression of proinflammatory mediators in macrophages. These results suggest a role for insulin resistance in macrophages in early atherosclerogenesis. (C) 2011 Elsevier Inc. All rights reserved.

 
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