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Inhibiting microRNAs Through ANTAGOMIRs

28.11.2008
An Experimental Strategy That Increases Vascularization And Reduces Infarct Size

What is a fruitful way to contain damages caused during an infarction? The answer is: trying to prevent/limit the action of damaging agents and promote the growth of new blood vessels that could help the recovery of damaged sites.

With this question (and answer) in mind, Stefanie Dimmeler Professor of Experimental Medicine and Head of the Molecular Cardiology at the University of Frankfurt and colleagues, set up their investigation on so-called microRNAs (miRNAs), small molecules involved in a number of critical processes including cardiovascular development, angiogenesis and inflammation.

During their study, the EVGN scientists identified a small group of promising miRNAs and developed an antagonist molecule called ANTAGOMIR that proved effective in blocking their noxious effects. These preliminary results were presented during the V Annual European Vascular Genomics Network Meeting held in Bad Hofgastein (Austria). Each year the Meeting convenes top scientists from all Europe and abroad, to discuss the state of the art and the most effective strategies and therapies in the field of Cardiovascular Disease (CVD).

miRNAs represent an attractive target for scientists who study CVD. Several investigations proved that they play a pivotal role, still to be defined, in cardiogenesis, cancer and in the regulation of complex processes. They are RNA molecules, but they do not carry any information useful for protein synthesis.

Their major role is to degrade specific mRNA molecules to prevent the assembly of selected proteins. Among their targets scientists have identified some proteins that promote angiogenesis (growth of blood vessels): when bound by miRNAs, these molecules are turned off and tissue damages can spread.

“The world of miRNAs is complex and articulated, so far several hundred molecules have been identified” underlined Stefanie Dimmeler in her presentation.

“Therefore we made a thorough screening and spotted a promising cluster in terms of activity on vessel remodelling and angiogenesis. When we checked for their presence we found that some of them were highly expressed in cells from patients with cardiac ischemia or coronary artery disease. This expression peaked at days 1-2 after ischemia. And other in vitro experiments suggested that these miRNAs hamper the repopulation of ischemic tissues by endothelial cells, a highly desirable event”.

So the scientists thought of developing an artificial molecule which was specular to the overall structure of some miRNAs, hence able to stick to them as the left and right hands of a person, in order to block their activity.

“We built an experimental ANTAGOMIR – said Dimmeler – in a way that it could adhere to several targets. The results were very promising, albeit still preliminary”. Some miRNAs were repressed – reported the researcher, and there was a good recovery of the heart functions in experimental laboratory models. “The extension of the infarcted site showed a significant reduction, paralleled by a restoration on the process of neovascularization”.

Now the German team plans to investigate in details if in the cluster analyzed there is one (or more) specific miRNA which is responsible of such effects, and to spot the molecular target(s) responsible for the therapeutic effects they observed.

For further information on this study please contact:
Cristina Serra
EVGN Press Office and Communication
cristina.serra@ifom-ieo-campus.it
Mobile: +39 338 4305210

Elena Bauer | alfa
Further information:
http://www.evgn.org/home
http://www.ifom-ieo-campus.it

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