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The little molecule that repairs your heart after a heart attack

Recent experiments in mice have demonstrated how a molecule of circular RNA called circCDYL might be able to help a heart repair itself after a heart attack by acting like a molecular sponge.

Image Credit: Source: PXHere

Chances are that you or someone you know has been affected by some form of heart disease. From cardiovascular disease to arrhythmias (abnormal heart beats) and maybe even a heart attack, these medical diagnoses are all too common among Americans. In the short term, heart disease can cause a lot of pain and discomfort. But in the long-term, heart disease can lead to serious heart damage and even more health issues. 

In more recent years, scientists have begun to investigate possible medical solutions that can help repair this heart damage. Ideally, scientists have been searching for a solution that uses the heart’s ability to heal itself to repair damage from a lack of nutrients or oxygen. One solution that has recently shown promise has been the use of a special biomolecule produced in the body called circular RNA. Circular RNA is made of a genetic material the body produces naturally (called RNA) that is bonded to itself, forming a ring-like structure. With this in mind, researchers from the Qingdao Medical Hospital system in China set out to investigate whether or not a special kind of circular RNA called circCDYL was effective at triggering the heart into repairing itself after a heart attack.

Scientists first set out to compare what effects circCDYL had on both healthy heart tissue and heart tissue that had recently undergone damage due to a heart attack. Researchers used mice for this experiment: young mice and adult mice. Using live mice, researchers took heart tissue samples from healthy mice and mice who had been injected with a special chemical that mimicked a heart attack. Researchers then  sampled healthy heart tissue and heart tissue which had suffered from hypoxia (lack of oxygen and nutrients). After their analysis, results revealed that there was less circCDYL in the diseased tissues than in the healthy tissues, regardless of the age of the mouse. 

Young mouse heart cells (left) that are healthy vs. adult mouse heart tissue with injury (right). The purple dots are immune cells repairing the tissue. Source: Kory J. Lavine and Douglas L. Mann

After observing this trend, researchers decided to increase the amount of circCDYL in young mice. Through genetic engineering of the mice’s genome, they increased the expression of circCDYL in the mice. After further analyzing the amount of healthy heart cells in the diseased mice, they found that increased levels of circCDYL increased the rate at which healthy heart cells were being made. In turn, the increased production of healthy cells began to replace the dead heart cells. The team also conducted an experiment where they decreased the amount of circCDYL present in healthy and sick mice. The results showed that the heart function in both young and old actually declined when circCDYL was taken out of the body. 

With this in mind, the research team decided to move on to adult mouse models in an attempt to compare the heart’s cell growth in older mice to the younger mice. The reason for this is that self-healing is often a much slower process as an animal gets older. After repeating the  experiments in older mice, the scientists discovered that an increase in circCDYL expression again led to increased healthy heart cell growth. In addition, low circCDYL levels decreased heart cell growth and overall heart cell health. Since these experiments were conducted in live mice, these results are more applicable to complex living systems. 

So how does circCDYL work? Scientists discovered that it was through circCDYL’s unique interaction with another special RNA material, called microRNA (miRNA), that caused healthy cells to grow. This special miRNA’s job is to pass on a message for cells to stop growing when they are injured. CircCDYL was found to bond very well to this messenger RNA, and therefore “soaked up” that RNA like a sponge, preventing it from relaying that very important message. This mechanism is new to genetic science and is aptly named a “molecular sponge mechanism.”  

Now that scientists have identified circCDYL as a circular RNA that can help repair and regulate heart cell growth, it’s only a matter of time before researchers begin to target this molecule for therapeutic purposes. If this science can be turned into a viable therapy, humans may once again be able to turn back the clock on our aging and injured hearts and gain a few more years with our loved ones.

Study Information

Original study: Circular RNA (circCDYL) CDYL Induces Myocardial Regeneration by ceRNA After Myocardial Infarction

Study was published on: June 11, 2020

Study author(s): Min Zhang, Zhen Wang, Qiushi Cheng, Zhihong Wang, Xiaobing Lv, Zhong Wang, Na Li

The study was done at: The Affiliated Hospital of Qingdao University

The study was funded by: "Departmental sources" from The Affiliated Hospital of Qingdao University

Raw data availability: Raw data not available.

Featured image credit: Source: PXHere

This summary was edited by: Jocelyn Solis-Moreira