MicroRNA may reduce stroke risk

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The molecule microRNA-210 stabilizes deposits in the carotid artery and can prevent them from tearing. Thus, it may prevent dangerous blood clots from forming. This is what scientists headed by Prof. Lars Mägdefessel, Professor of Vascular Biology at the Technical University of Munich (TUM) and head of a junior scientist group in the German Centre for Cardiovascular Research (DZHK) have discovered. Their results open new treatment approaches to reduce stroke risk in patients with carotid arteries at risk of rupturing.

Carotid artery disease:

Most common cause of carotid artery disease is atherosclerosis, where so-called plaques build up on the vessel walls. If a plaque ruptures, blood clots can form that either further occlude the site that is already narrowed or is carried away by the blood flow, which could lead to vascular occlusion at a different site. When this happens in the carotid artery, it could lead to stroke. How easily a plaque ruptures depends on the thickness of the tissue layer surrounding its core, called as fibrous cap-  more stable and therefore harmless the vessel deposit.

Stabilizing instead of reducing

“New imaging procedures enable us to detect dangerous plaques with increasing precision; but the therapies currently available for removing these unstable plaques and thus preventing a stroke entail a certain amount of risk that the plaques will rupture during the procedure”, explains Lars Mägdefessel. “This is why these therapies are not used on individuals with a narrowed carotid artery who have so far not experienced any symptoms.”

Traditionally, physicians try to reduce the size of the deposits in the vessels to widen the narrowed sites. “For narrowed carotid arteries, though, the notion of stabilizing the plaques is becoming ever more prevalent. Unlike in the coronary vessels, in the carotid artery plaques rupturing is more dangerous than the narrowing”, says Mägdefessel.

Local application is crucial

The scientists are currently researching how microRNA-210 can be applied locally. The risk of adverse events in other organs is much too high if microRNA modulators are administered systemically. The main concern with microRNA-210 is that tumor cells that are possibly already in existence will multiply because the expression of APC is inhibited. This is because APC is a tumor suppressor gene which inhibits the growth of cancers in the healthy body.

In order to avoid such so-called off-target effects, the researchers are currently testing coated stents or balloons that are inserted directly into the carotid artery in pigs. “For this step, we also rely on the collaboration with companies that, for example, develop soft balloons that cause little friction and thus make the procedure safer”, says Mägdefessel. “Only thus will our results reach patients as effective therapies.”