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An Alternative to Bypass Surgery: a Gene Silencer that Induces Anti-Inflammatory Macrophages and Prevents Atherosclerosis.

Jan 25, 2016 1:00:40 PM / by Dalia Gaddis

 A microRNA - or gene silencer - in macrophages can offer a new potential therapy that can replace coronary bypass surgery. Image Credit: https://commons.wikimedia.org/wiki/File:Coronary_artery_bypass_surgery_Image_657B-PH.jpgResearchers find a microRNA that can alter macrophages from pathogenic M1 to anti-inflammatory M2 and protects against atherosclerosis.

We all know someone who has gone through a coronary artery bypass graft or, as commonly known, a bypass surgery. It starts with too much fat and cholesterol accumulating in and narrowing the arteries and ends with a relatively complicated surgical procedure where one or more arteries in the heart get replaced by another coming from the patient’s chest or leg. While the mortality rate due to the procedure is only at 2-4%, there are multiple risks involved with the surgery, and these risks increase further with additional complications, such as diabetes, obesity, or poor general health. It is estimated that in the U.S. more than 500,000 patients undergo a coronary bypass surgery with a rough cost of 30 billion dollars each year1.

Atherosclerosis - or the process of narrowing of blood vessels due to fat deposits - is not merely a physical process of excess fat and cholesterol depositing on the vessel walls, but a more dynamic immune cell-mediated one. In this process, M1 macrophages, in an attempt to get rid of extra fat, take up fat molecules, swell up, and become foam cells. These foam cells secret multiple factors that signal danger, recruiting other cells to the vessels. The recruited cells release inflammatory cytokines, and the process repeats itself, ultimately leading to calcification and the narrowing of the vessels. Research has been trying to find ways to reduce atherosclerosis, or plaque formation, through altering lipid metabolism and excretion as well as immune system regulation.

In a recent article published in the Journal of Clinical Investigation, a group of researchers from NYU School of Medicine found that a microRNA (miR-33) played an important role in the process of atherosclerosis. Researchers treated mice that were fed a high cholesterol diet with anti-miR-33, a small gene silencer that affects how cholesterol gets out of the cells. Following 8 weeks of treatment, the researchers observed a reduction in the plaque formation and atherosclerosis incidence in the mice. They investigated the reason for protection and found that in the anti-mir33 treated mice, macrophages' metabolism changed, switching them from pathogenic M1 to more anti-inflammatory protective M2 macrophages. This change to M2 macrophages also promoted the development of another set of protective cells, regulatory T cells, which inhibit inflammatory mediated T cell responses2.

So is the need for coronary bypass surgery really gone? Not yet! Researchers are still trying to figure out how to use miRNA therapeutically in patients. Issues with side targets and specific delivery still need to be addressed. But with the constantly improving gene delivery and targeting technology, the promise is high. Here at HemaCare, we provide M1, M2 macrophages and regulatory T cells that can be used to study atherosclerosis or other macrophage-driven diseases. We will be following enthusiastically how gene-silencing therapeutics using microRNA and other gene regulators unfold in the coming years.

References:

1 http://www.medscape.com/viewarticle/434471_11

2 Ouimet M. et al. (2015). MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. Journal of Clinical Investigation, 125 (12), doi:10.1172/JCI81676.

Topics: Cardiovascular Disease, Macrophages, Regulatory T Cells, Basic Research

Dalia Gaddis

Written by Dalia Gaddis

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