Cardiovascular disease is the number-one killer worldwide, but the discovery of a noncoding RNA that holds back the regeneration of heart muscle cells could lead to new treatment options.
© SEBASTIAN KAULITZKI/Science Photo Library/Getty
Researchers at A*STAR have identified the ‘brakes’ that keep heart muscle cells from dividing and healing damaged heart tissue. This finding raises the possibility of developing treatments that target these brakes to stimulate heart repair.
More people die of cardiovascular disease than of any other cause. One reason the disease is so often fatal is that heart muscle cells, or cardiomyocytes, are very slow to divide and replenish themselves. Consequently, damage to the heart is often irreversible. Scientists have long searched for a way to induce cardiomyocytes to regenerate at higher rates.
Now, Roger Foo and his co-workers at the A*STAR Genome Institute of Singapore have identified the culprit responsible for the slow regeneration rates of cardiomyocytes — a long noncoding ribonucleic acid (RNA) the team labeled ‘SingHeart’.
Noncoding RNA does not code for proteins and previously had no known useful role, leading some to call it ‘junk RNA’. But there is now recognition that noncoding RNA plays an important role in modifying the expression of genes that code for proteins. In the case of SingHeart, Foo and co-workers found that the noncoding RNA regulates genes that control the ability of cardiomyocytes to multiply.
“This finding has the potential to change forever the way heart failure patients are treated,” comments Foo. “Right now, drugs for patients with cardiovascular disease only stem the progress of the disease. Regenerative treatments that target SingHeart could reverse the course of the disease, which would be a revolutionary way to treat heart failure.”
The researchers discovered SingHeart by analyzing gene expression in single cardiomyocytes derived from healthy and diseased hearts of both mice and humans. Their analysis revealed that, in diseased hearts, certain cardiomyocytes activate genetic programs related to cell division — the first time that different subpopulations of cardiomyocytes have been shown to have different gene expression in response to stress. Further analysis showed that SingHeart plays a role in blocking genes responsible for cell division in cardiomyocytes.
The team is now exploring whether this finding can be used to develop new treatments for cardiovascular disease. “We’re very hopeful this will lead to future clinical treatments,” says Foo. “If not through SingHeart, then through other molecules that my team are also hunting for.”
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore.
