Researchers at the University of Bristol, England, School of Clinical Services, have found that one of the smallest entities in the human genome, microRNA (miRNA), could increase the risk of limb amputation in diabetic patients who have poor circulation. Their experimental cell study shows that conditions mimicking diabetes and a lack of blood supply to a tissue increased a particular miRNA, miRNA-503, and impaired the ability of the endothelial cells, which line the interior surface of blood vessels, to duplicate and form into networks of small blood vessels. miRNA-503 reduces cell growth and prevents the formation of blood vessels by direct binding and inhibition of cyclin E1 (CCNE1), a protein that has been found to have crucial roles in cell proliferation and oncogenesis, and the cell cycle-regulatory Cdc25 mRNA phosphatase.
Alternatively, slowing down miRNA-503 improved the endothelial cells’ duplication process. By using mouse models of diabetes and limb ischemia, the researchers found that inhibition of the miRNA-503 (using a “decoy miRNA”) could restore post-ischemic blood flow recovery.
“Because each miRNA 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,” Constanza Emanueli, PhD, professorial research fellow in vascular pathology and regeneration, said. “Our study is the first to provide evidence for a role of miRNAs in diabetes-induced defects in reparative angiogenesis.”
The study, which was conducted by research assistant Andrea Caporali, PhD, and colleagues in a regenerative medicine research group led by Emanueli, PhD, was funded by the Medical Research Council and the British Heart Foundation and is published online in Circulation: Journal of the American Heart Association.
Editor’s note: This story has been adapted from materials provided by the University of Bristol, England.