Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

摘要: PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of shortage. However, it is unknown whether can influence arteriogenesis. Here we studied the role collateral artery growth using hindlimb ischaemia a model, process compensates for lack flow major arterial occlusion. We show Phd2 (also known Egln1) haplodeficient (Phd2(+/-)) mice displayed preformed arteries preserved limb perfusion prevented tissue necrosis ischaemia. Improved arteriogenesis Phd2(+/-) was due to expansion tissue-resident, M2-like macrophages their increased release arteriogenic factors, leading enhanced smooth muscle cell (SMC) recruitment growth. Both chronic acute deletion one allele sufficient skew polarization towards pro-arteriogenic phenotype. Mechanistically, preconditioning relied on activation canonical NF-κB pathway macrophages. These results unravel how regulates homeostasis controlling specific differentiation state suggest new treatment options ischaemic disorders.