Lei Lv1, Wei Liang1, Meng Ye1, Jiwei Zhang1, Hao Zhang1, Guanhua Xue2, Lan Zhang3. 1. Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: pudongnanlu@sohu.com. 3. Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: rjzhanglan@sjtu.edu.cn.
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. METHODS AND 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. CONCLUSION: Collectively, these data highlight the significance of Thbs4 in regulating macrophage accumulation and treating restenosis.
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. METHODS AND 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. CONCLUSION: Collectively, these data highlight the significance of Thbs4 in regulating macrophage accumulation and treating restenosis.
Authors: Samuel Röhl; Urszula Rykaczewska; Till Seime; Bianca E Suur; Maria Gonzalez Diez; Jesper R Gådin; Anastasiia Gainullina; Alexey A Sergushichev; Robert Wirka; Mariette Lengquist; Malin Kronqvist; Otto Bergman; Jacob Odeberg; Jan H N Lindeman; Thomas Quertermous; Anders Hamsten; Per Eriksson; Ulf Hedin; Anton Razuvaev; Ljubica Perisic Matic Journal: JVS Vasc Sci Date: 2020-02-07
Authors: Vincent Ten Cate; Thomas Koeck; Jürgen Prochaska; Andreas Schulz; Marina Panova-Noeva; Steffen Rapp; Lisa Eggebrecht; Michael Lenz; Julia Glunz; Madeleine Sauer; Raff Ewert; Michael Halank; Thomas Münzel; Stefan Heitmeier; Miguel A Andrade-Navarro; Karl J Lackner; Stavros V Konstantinides; Kirsten Leineweber; Philipp S Wild Journal: Blood Adv Date: 2021-07-27