Syndicate content

Specific MicroRNA May Help Initiate Inflammation in Atherosclerosis

Atherosclerosis – otherwise known as hardening of the arteries – is a prevalent cause of death in modern societies. The condition arises from the build-up of localized fatty deposits called plaques in the arteries. Macrophages, the phagocytic cells of the immune system, migrate to these sites, inducing chronic inflammation which exacerbates the accumulation of the atherosclerotic lesions. These can lead to obstruction of major vessels, causing heart attack and stroke. A team of medical researchers led by Ludwig Maxmillians University (LMU) Professor Andreas Schober in Munich, Germany has now identified a particular microRNA (miRNA) that helps initiate the inflammatory process. The work was published online on March 19, 2013 in Circulation. miRNAs are short segments of RNA derived from longer precursors transcribed from defined stretches of the genomic DNA. The miRNAs act as versatile regulators of gene expression in cells, and also control the function of macrophages, in which patterns of gene activity must respond rapidly to changes in the extracellular environment. “However, the miRNAs that control the inflammation process during the various stages of atherosclerosis had not been identified up to now,” says Professor Schober. In an earlier study, Professor Schober and his team had shown that the microRNA miR-155 is a prominent member of the miRNA population in macrophages. The molecule prevents the synthesis of a protein that inhibits the inflammatory reaction, and thus promotes the progression of atherosclerosis. However, miR-155 does not serve as the initiator of inflammation. Professor Schober and his colleagues have now looked at the patterns of microRNA expression in atherosclerotic lesions in the mouse, and noted that levels of a different miRNA, called miR-342-5p, increase in very early plaques. “The newly identified miR-342-5p is actually expressed constituitively in macrophages, but it is activated by pro-inflammatory signals. This activation process then induces production of miR-155,” Professor Schober explains. The results of the new study thus make miR-342-5p an interesting target for new therapeutic agents. Indeed, in their animal model, the researchers have been able to demonstrate that inhibition of the action of miR-342-5p by means of a specific antagonist retards the progression of atherosclerosis. “Atherosclerosis in humans should also be susceptible to treatment with inhibitors of microRNAs,” Professor Schober suggests. “Synthetic inhibitors are available for each and every microRNA, and could be used for therapeutic purposes as soon as their efficacy and safety has been demonstrated in clinical tests.” Hence the researchers now plan to collaborate with biotechnology companies on the development of their own specific microRNA inhibitor for future clinical use. [Press release] [Circulation abstract]