Inhibition of hyperglycemia-induced angiogenesis and breast cancer tumor growth by systemic injection of microRNA-467 antagonist

Abnormal angiogenesis in multiple tissues is a key characteristic of the vascular complications of diabetes. However, angiogenesis may be increased in one tissue but decreased in another in the same patient at the same time point in the disease. The mechanisms of aberrant angiogenesis in diabetes are not understood. There are no selective therapeutic approaches to target increased neovascularization without affecting physiologic angiogenesis and angiogenesis in ischemic tissues. We recently reported a novel miRNA-dependent pathway that up-regulates angiogenesis in response to hyperglycemia in a cell- and tissue-specific manner. The goal of the work described herein was to test whether systemic administration of an antagonist of miR-467 would prevent hyperglycemia-induced local angiogenesis in a tissue-specific manner. We examined the effect of the antagonist on hyperglycemia-induced tumor growth and angiogenesis and on skin wound healing in mouse models of diabetes. Our data demonstrated that the systemic...