title: Thrombospondin-4 ablation reduces macrophage recruitment in adipose tissue and neointima and suppresses injury-induced restenosis in mice.
abstract: OBJECTIVE
  Thrombospondin-4 (Thbs4) is a member of the extracellular calcium-binding protein family and is linked to cell adhesion and migration. Given the involvement of Thbs4 in vascular inflammation, we hypothesized that Thbs4 plays a role in restenosis.
  
  
  RESULTS
  Here we show evidence that Thbs4 is upregulated in wire-injured mouse arteries and correlated with CD68 expression. Macrophage infiltration is reduced in both adipose tissue (AT) and neointima of Thbs4/ApoE double knockout (DKO) mice after injury. Moreover, Thbs4 deficiency prevents restenosis in ApoE KO mice fed a Western-type diet (WTD). Lethally irradiated DKO mice that receive bone marrow from ApoE KO or DKO mice have reduced neointima development. While considering related mechanisms, we note decreased chemokine production in both AT and neointima of DKO mice. In addition, vascular smooth muscle cells (VSMCs) derived from DKO mice display suppressed proliferation and migration in comparison with controls. Thioglycollate (TG)-induced macrophages from DKO mice show retarded adhesion to VSMCs. Recombinant Thbs4 promoted macrophage adhesion to VSMCs, and enhanced VSMC proliferation and migration.
  
  
  CONCLUSIONS
  Collectively, these data highlight the significance of Thbs4 in regulating macrophage accumulation and treating restenosis.
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Lei
authors: L
authors: Lv
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Wei
authors: W
authors: Liang
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Meng
authors: M
authors: Ye
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Jiwei
authors: J
authors: Zhang
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Hao
authors: H
authors: Zhang
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: pudongnanlu@sohu.com.
authors: Guanhua
authors: G
authors: Xue
authors: Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: rjzhanglan@sjtu.edu.cn.
authors: Lan
authors: L
authors: Zhang
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D058426:Neointima; D010641:Phenotype; D012008:Recurrence; D019699:Thrombospondins / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D066253:Vascular Remodeling; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D019699:Thrombospondins; C101864:thrombospondin 4
keywords: Adipose tissue; Macrophage; Restenosis; Thrombospondin-4