Abstract 821: HSPA12B is a Novel Angiogenesis Regulator
We recently cloned HSPA12B, a new member of HSP70 family. The HSP70 family encodes molecular chaperones and participates in cellular stress response. It has been reported that HSP70 is induced by ischemia and protects mice against ischemia-reperfusion injury. Angiogenesis is one major protective mechanism against ischemic injury. In this study, we showed that HSPA12B was strongly and predominantly expressed in endothelial cells lining blood vessels by in situ hybridization, immunostaining, and reporter mice. HSPA12B was preferentially localized in cytoplasm, similar to that of HSP70. In a Matrigel assay, angiogenesis was inhibited in human umbilical vein endothelial cells in the presence of HSPA12B-neutralizing antibodies and by HSPA12B RNAi knock-down. This indicated that HSPA12B was required for angiogenesis. Cell migration is an important step during angiogenesis, and HSPA12B mediated angiogenesis during migration, since neutralizing HSPA12B proteins reduced cell migration in a migration assay. To further characterize the mechanism, we identified multiple HSPA12B-interacting proteins through yeast two-hybrid screening, co-immunoprecipitation and co-localization assays. HSPA12B bound to, and negatively regulated the level of, SSeCKS, a protein known to inhibit angiogenesis and promote tight-junction formation. HSPA12B was induced in human aortic endothelial cells under shearing, in ischemic mouse heart, and in atherosclerotic lesions. In conclusion, our study provides the first evidence that HSPA12B is an endothelia-specific chaperone, a regulator of angiogenesis, and a potential therapeutic target for angiogenesis-related diseases.