MicroRNAs could increase amputation risk in diabetics

WASHINGTON - A new study has discovered that micro-RNA, one of the smallest entities in the human genome, could increase the risk of limb amputation in diabetic patients who have poor blood flow.

Andrea Caporali and colleagues 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 a particular miRNA (miRNA-503) and impaired the ability of endothelial cells, which line the interior surface of blood vessels.

Micro-RNAs (miRNAs) are small sections of ribonucleic acid (RNA) that can inhibit many genes.

Alternatively, slowing down miRNA-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.

The team subsequently investigated miR-503 and target gene expression in muscular specimens from the amputated ischaemic legs of diabetic patients.

As controls, calf biopsies of non-diabetic and non-ischemic patients undergoing saphenous vein stripping were used. In diabetic muscles, miR-503 expression was remarkably higher, and plasma miR-503 levels were also elevated in the diabetic subjects.

Finally, using mouse models of diabetes and limb ischaemia, the researchers found that inhibition of the miRNA-503 (using a “decoy miRNA”) could restore-post-ischaemic blood flow recovery.

The study has been published online in Circulation: Journal of the American Heart Association. (ANI)