MicroRNAs could increase the risk of amputation in diabetics

Jan 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 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 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 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-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 ") could restore-post-ischaemic blood flow recovery. The findings of this study highlight important clinical implications of miR-503 in diabetes-associated vascular complications.

In early diabetes, high blood glucose levels damage leading to lack of blood flow (ischaemia). Such ischaemic 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 , the ischaemic disease follows an unalterable course and is too often the eventual remedy.

Tissues can recover from lack of by new blood vessel growth (angiogenesis), which restores blood supply to the tissue (reperfusion). However, diabetes harms the restoration of the flow of blood to a previously ischemic tissue, by mechanisms that are not fully understood, and so a better understanding of the molecular mechanisms underpinning diabetes-associated vascular complications is urgently needed to improve therapeutic options.

Explore further: US scientists make embryonic stem cells from adult skin

More information: Deregulation of microRNA-503 contributes to diabetes-induced impairment of endothelial function and reparative angiogenesis after limb ischemia, Andrea Caporali, Marco Meloni, Christine Völlenkle, Desiree Bonci, Graciela B Sala-Newby, Roberta Addis, Gaia Spinetti, Sergio Losa, Rachel Masson, Andrew H Baker, Reuven Agami, Carlos le Sage, Gianluigi Condorelli, Paolo Madeddu, Fabio Martelli, Costanza Emanueli, Circulation, published online January 10, 2011.

add to favorites email to friend print save as pdf

Related Stories

Human stem cells promote healing of diabetic ulcers

Apr 20, 2009

(PhysOrg.com) -- Treatment of chronic wounds is a continuing clinical problem and socio-economic burden with diabetic foot ulcers alone costing the NHS £300 million a year. Scientists in Bristol have found ...

Importance of cell-cell communication

Jun 29, 2010

A team from the Bristol Heart Institute have investigated the importance of cell-cell communication in regulating the formation of new blood vessels following the restriction in blood supply to the heart or back leg in mice.

Gene therapy and stem cells save limb

Dec 08, 2009

Blood vessel blockage, a common condition in old age or diabetes, leads to low blood flow and results in low oxygen, which can kill cells and tissues. Such blockages can require amputation resulting in loss of limbs. Now, ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

UAE reports 12 new cases of MERS

Health authorities in the United Arab Emirates have announced 12 new cases of infection by the MERS coronavirus, but insisted the patients would be cured within two weeks.

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...