Researchers at the University of Bristol have shown in an experimental cell study that conditions mimicking diabetes and a lack of blood supply to a tissue increased microRNA-503 and impaired the ability of endothelial cells, which line the interior surface of blood vessels.
Alternatively, slowing down microRNA-503 improved the capability of endothelial cells to duplicate and form into networks of small blood vessels. The researchers showed that microRNA-503 reduces cell growth and prevents the formation of blood vessels by direct binding and inhibition of cyclin E1 and Cdc25 mRNA.
Finally, using mouse models of diabetes and limb ischaemia, the researchers found that inhibition of the microRNA-503 (using a “decoy miRNA”) could restore-post-ischaemic blood flow recovery. The findings of this study highlight important clinical implications of microRNA-503 in diabetes-associated vascular complications.
Costanza Emanueli, Professorial Research Fellow in Vascular Pathology & Regeneration – “Because each microRNA can regulate many genes, they represent an exciting new target to correct diseases that have complex underlying mechanisms, like diabetes, rather than trying to target one specific gene. Our study is the first to provide evidence for a role of miRNAs in diabetes-induced defects in reparative angiogenesis.”
Caporali A, Meloni M, Völlenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, le Sage C, Condorelli G, Madeddu P, Martelli F, Emanueli C. (2011) Deregulation of microRNA-503 Contributes to Diabetes Mellitus-Induced Impairment of Endothelial Function and Reparative Angiogenesis After Limb Ischemia. Circulation [Epub ahead of print]. [abstract]