An acyl pyrrole compound 361B promotes angiogenesis and improves hindlimb ischemia recovery

Diabetes is the most common type of chronic diseases word wide, accompanied by inadequate local angiogenesis and vascular lesions which is characterized by a gradual disorder function of the endothelial cells. Vascular complications which includes lower limb ischemia and chronic wound healing, are the main cause of death and disability in diabetic patients. Previous evidence has shown that restoring angiogenesis function of endothelial cells was detected as a key treatment project of diabetic complications. However, there is no specific medicine to treat the above diseases currently. Here, we make an effort to develop a new small molecule compound that promotes angiogenesis. To do this, we screen a library of small molecules and identify compound 361B, which significantly promote endothelial cell sprouting, tube formation, microvessels formation from aortic ring and neovascularization in mouse corneal. Moreover, 361B enhances the ability of angiogenesis in a diabetic mouse hindlimb ischemia model and a wound model. Meanwhile, 361B prevented HUVECs from starvation-induced apoptosis. Through Pull-down assays and SPR experiments, we have confirmed that 361B directly binds to vimentin in endothelial cells. Finally, it has been demonstrated through QPCR and Western Blotting Assay that 361B activates Akt/eNOS pathway to promote angiogenesis. As a conclusion, our data proves that 361B could be considered as a promising compound with the potential to treat diabetic vascular complications.