Abstract 11779: Tie2-Expressing Macrophages Induced by PHD2 Haplodeficiency Prevents Ischemic Damage After Limb Ischemia and Myocardial Infarction by Inducing Collateral Artery Growth

We already demonstrated that heterozygous deficiency of PHD2 oxygen sensor promotes vessel stabilization and maturation, thus increasing oxygen supply. Thus, we investigated the role of PHD2 in ischemia. Despite femoral artery ligation, PHD2+/- mice displayed nearly normal perfusion of the lower limb that prevented the ischemic damage of the muscle and preserved the running performance. The same was true in a mouse model of myocardial infarction. We found that, at baseline, collateral arteries in PHD2+/- mice were more functional, larger, and surrounded by a thicker media layer, altogether allowing the blood flow to bypass the occlusion point. Quantitative PCR analysis of PHD2+/- peritoneal macrophage showed the mRNA level of Tie2 was significantly up-regulated together with other arteriogenic M2 genes including Arginase1, CXCR4, CCR2, HGF, PDGF-B, FIZZ, Neuropilin1, and SDF1 when compared to WT. Smooth muscle cells (SMCs) were chemoattracted 10 times more potently towards PHD2+/- than WT macrophages in v...