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Micro-RNAs Retard Development of Atherosclerosis in Early Studies

Researchers see potential for nanoparticle therapy

Medical researchers in Germany have shown that the administration of specific micro-RNAs can retard the development of atherosclerosis. Atherosclerosis develops primarily at sites in the arterial vasculature where endothelial cells, which form the inner lining of blood vessels, are particularly susceptible to damage.

“Where blood-flow is perturbed and other risk factors are present, such as hyperlipidemia with abnormally high levels of cholesterol, the cells of the endothelium mount a stress reaction, which can result in programmed cell death but also in increased proliferation of endothelial cells,” explained Professor Christian Weber of Ludwig Maximilian University in Munich.

The significance of this increased cell turnover for the regeneration of the endothelium and the development of atherosclerosis has, however, remained unclear. A research team led by Weber and Professor Andreas Schober has elucidated the role of two microRNAs — miR-126-3p and miR-126-5p — in the process. Their findings were reported in Nature Medicine.

MicroRNA strands play important roles in the regulation of gene activity. miR-126-5p and miR-126-3p are complementary sister strands that are derived from the same precursor RNA.

“We have now shown, for the first time, that the repair of the endothelium after injury, and the regenerative proliferation of endothelial cells, is induced by miR-126-5p, which specifically inhibits production of the protein Dlk1 (Delta-like 1),” Schober said. In the absence of miR-126-5p, deposits accumulate at sites in the vascular system where potentially proliferative endothelial cells are normally held in reserve to compensate for any damage that may occur.

In a mouse model, the researchers demonstrated that the administration of miR-126-5p could prevent the development of athersclerotic lesions. “As soon as the levels of miR-126-5p are increased, the proliferative reserve of endothelial cells is restored, which protects the animals against atherosclerosis,” Schober explained.

The results of their study are relevant for future approaches to the treatment of atherosclerosis, the researchers say. Both synthetic inhibitors and functional mimics of micro-RNAs are available, which can be administered by injection.

“Our data suggest that the therapeutic application of miR-126-5p mimics holds promise for the treatment of atherosclerosis patients,” Weber commented. In their studies in mice, he and his team have tried a new mode of administering these agents, in which nanoparticles are used to deliver miR-126-5p to the affected tissue.

“In view of the protective effects of miR-126-3p, it might even be worthwhile to use a combination of the two strands,” Weber added. He is currently testing this strategy.

Source: Medical Xpress; March 6, 2014.

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