Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Tan, Xiaoyong; Yan, Kai; Ren, Meiping; Chen, Ni; Li, Yongjie; Deng, Xin; Wang, Liqun; Li, Rong; Luo, Mao; Liu, Yong; Liu, Yan; Wu, Jianbo
• Is Part Of: Journal of translational medicine. Volume 14:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Angiopoietin-2 -- Ischaemia -- Arteriogenesis -- Macrophage; Medicine, Experimental -- Periodicals; Human experimentation in medicine -- Periodicals; Therapeutics -- Periodicals; 615.50724
• DOI: 10.1186/s12967-016-1055-x
• Languages: English
• ISSNs: 1479-5876

Abstract

Abstract Background 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. Methods 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. Results 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. Conclusions Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration.