title: Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia.
abstract: Angiopoietin-2 (Ang-2), a ligand of the Tie-2 receptor, plays an important role in maintaining endothelial cells and in destabilizing blood vessels. Collateral artery growth (arteriogenesis) is a key adaptive response to arterial occlusion. It is unknown whether the destabilization of blood vessels by Ang-2 can affect arteriogenesis and modulate mononuclear cell function. This study aimed to investigate the effects of Ang-2 on collateral artery growth.
  
  
  
  Hindlimb ischaemia model was produced in C57BL/6 mice by femoral artery ligation. Blood flow perfusion was measured using a laser Doppler perfusion imager quantitative RT-PCR analysis was applied to identify the level of angiogenic factors.
  
  
  
  After the induction of hindlimb ischaemia, blood flow recovery was impaired in mice treated with recombinant Ang-2 protein; this was accompanied by a reduction of peri-collateral macrophage infiltration. In addition, quantitative RT-PCR analysis revealed that Ang-2 treatment decreased monocyte chemotactic protein-1 (MCP-1), platelet-derived growth factor-BB (PDGF-BB) mRNA levels in ischaemic adductor muscles. Ang-2 can lead to macrophage M1/M2 polarization shift inhibition in the ischaemic muscles. Furthermore, Ang-2 reduced the in vitro inflammatory response in macrophages and vascular cells involved in arteriogenesis.
  
  
  
  Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration.
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Xiaoyong
authors: X
authors: Tan
authors: Renshou People's Hospital, Renshou, Sichuan, China.
authors: Kai
authors: K
authors: Yan
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Meiping
authors: M
authors: Ren
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Ni
authors: N
authors: Chen
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Yongjie
authors: Y
authors: Li
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Xin
authors: X
authors: Deng
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Liqun
authors: L
authors: Wang
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Rong
authors: R
authors: Li
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Mao
authors: M
authors: Luo
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Yong
authors: Y
authors: Liu
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
authors: Yan
authors: Y
authors: Liu
authors: Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China. wuji@missouri.edu.|Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. wuji@missouri.edu.|Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO, USA. wuji@missouri.edu.
authors: Jianbo
authors: J
authors: Wu
mesh_terms: D042702:Angiopoietin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D042702:Angiopoietin-2; D011994:Recombinant Proteins
keywords: Angiopoietin-2; Arteriogenesis; Ischaemia; Macrophage