Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia.
Tan X1,2, Yan K3, Ren M1,2, Chen N1,2, Li Y1,2, Deng X1,2, Wang L1,2, Li R1,2, Luo M1,2, Liu Y1,2, Liu Y1,2, Wu J4,5,.
Author information
· 1Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.
· 2Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
· 3Renshou People's Hospital, Renshou, Sichuan, China.
· 4Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China. wuji@missouri.edu.
· 5Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
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.
