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MicroRNAs could increase the risk of amputation in diabetics
Date:1/12/2011

New research has found one of the smallest entities in the human genome, micro-RNA, could increase the risk of limb amputation in diabetic patients who have poor blood flow.

The study by Dr Andrea Caporali and colleagues in Professor Costanza Emanueli's research group in the Regenerative Medicine Section of the School of Clinical Sciences at the University of Bristol was funded by the Medical Research Council and is published online in Circulation: Journal of the American Heart Association.

The research group 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.

Costanza Emanueli, Professorial Research Fellow in Vascular Pathology & Regeneration, said: "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. Our study is the first to provide evidence for a role of miRNAs in diabetes-induced defects in reparative angiogenesis."

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-50
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Contact: Joanne Fryer
joanne.fryer@bristol.ac.uk
44-117-331-7276
University of Bristol
Source:Eurekalert

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