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Micro-RNAs could potentially increase amputation risk in patients with diabetes
Caporali A. Circulation. 2011:doi:CIRCULATIONAHA.110.003855v1-CIRCULATIONAHA.110.003855.
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New research has found that one of the smallest entities in the human genome, micro-RNA, could increase the risk for limb amputation in patients with diabetes who have poor blood flow.
The study by Andrea Caporali, MSc, PhD, research assistant and colleagues in the regenerative medicine section of the School of Clinical Sciences at University of Bristol, U.K., 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 said in an interview. “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, endothelial cells do not express miR-503. Unfortunately, diabetes induces miR-503 expression in endothelial cells, 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, the researchers said.
“In diabetic patients, the ischemic disease follows an inexorable course, so that limb amputation is often the ultimate remedy for unbearable symptoms,” Caporali said. “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.”
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