Micro-RNAs Could Potentially Increase Risk of Amputation in Diabetics

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 Andrea Caporali, MSc, PhD, research assistant and colleagues in Costanza Emanueli’s, PhD 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.

The research group has shown in an experimental cell study that conditions mimicking diabetes and a lack of blood supply to a tissue increased a particular Micro-RNA (miRNA) and impaired the ability of endothelial cells, which line the interior surface of blood vessels.

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.

“Diabetes impairs blood perfusion and the reparative capacity of ischemic limb muscles,” Caporali told O&P Business News. “This may determine very serious complications, including the formation of non-healing skin ulcers, which require foot or limb amputation. A defect in survival and function of the endothelial cells which line the blood vessels is at the basis of these diabetes complications. We discovered that the presence of the miR-503 is able to inhibit the proliferation of endothelial cells repressing cell cycling associated genes. In healthy blood vessels, ECs do not express miR-503. Unfortunately, diabetes induces miR-503 expression in ECs, thus preventing the growth of new blood vessels necessary to compensate for ischemia.”

The findings of this study highlight important clinical implications of miR-503 in diabetes-associated vascular complications.

“In diabetic patients, the ischemic disease follows an inexorable course, so that limb amputation is often the ultimate remedy for unbearable symptoms,” Caporali explained. “Better understandings of the molecular mechanisms underpinning diabetes microvascular complications are urgently needed to improve therapeutic options. Manipulation of miRNAs represents a novel approach to interfere with gene regulation, thus opening new avenues for molecular therapeutics. The results from this proposal provided new insights into the role of miRNAs in diabetes-induced microangiopathy and impaired angiogenesis.”

In early diabetes, high blood glucose levels damage blood vessels leading to lack of blood flow. Such ischemic complications are the leading cause of disease and death in diabetic patients. In limbs, lack of blood flow can result in non-healing ulcers and, in diabetic patients, the ischaemic disease follows an unalterable course and limb amputation is too often the eventual remedy.

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