Annexin A2 Promotes Angiogenesis After Ischemic Stroke Via Annexin A2 Receptor - AKT/ERK Pathways

Abstract Promoting angiogenesis to restore circulation to the ischemic tissue is still an important therapeutic target in stroke. Here, we ask whether the Ca2+-regulated, phospholipid-and membrane-binding protein-Annexin A2 (ANXA2) may regulate angiogenesis after stroke.Compared with wild type (WT) mice, the density of microvessels in brain and the number of new vessels sprouting from aortic ring were significantly increased in Anxa2 knock-in (ANXA2+/+) mice. After focal cerebral ischemia, proliferation of brain endothelial cells in ANXA2+/+ mice was significantly elevated at 7 days post-stroke, which further improved behavioral recovery. To assess the pro-angiogenic mechanisms of ANXA2, we used brain endothelial cells cultures to investigate its effects on cell tube-formation and migration. Recombinant ANXA2 increased tube-formation and migration of brain endothelial cells either under normal condition or after OGD injury. These protective effects of recombinant ANXA2 were regulated by interaction with ANXA2 receptor (A2R), and the ability of ANXA2-A2R to activate AKT/ERK pathways. Taken together, our study indicates that ANXA2 might be involved in angiogenesis after ischemic stroke. Further investigation of ANXA2-A2R will provide a new therapeutic target for stroke.