A protein called cardiotrophin 1 might be an effective treatment for heart failure, according to researchers who found that it tricks the heart into growing in a healthy way. This growth is reversible, similar to that which occurs in response to endurance exercise or pregnancy.
The team, including members from the Ottawa Hospital and the University of Ottawa in Ontario, Canada, reports the finding in the journal Cell Research.
The study paper also describes how, in animal models of heart failure, cardiotrophin 1 (CT1) promotes heart repair and improves blood flow.
Heart failure is a serious condition in which the heart cannot pump enough oxygen-rich blood to meet the needs of the body and its organs. The condition commonly results from heart muscle damage following a heart attack, the main cause of which is coronary artery disease.
There are around 26 million people living with heart failure worldwide, and numbers are rising.
The outlook for patients diagnosed with heart failure are poor; their survival rates are worse than those of patients with breast, prostate, and bowel cancer.
In the United States – where around 5.7 million adults are living with heart failure – around half of patients die within 5 years of being diagnosed.
If heart failure is diagnosed and treated early, it is possible to improve survival and quality of life. Treatment usually consists of drug therapy, reducing dietary sodium, and exercising regularly.
The new study represents a step forward in a regenerative medicine approach to the treatment of heart failure, where the aim is to treat or even cure the disease by regrowing damaged tissue or restoring function.
Co-senior study author Lynn Megeney, a professor at the University of Ottawa, explains that when part of the heart dies – as it does in heart failure – “the remaining muscles try to adapt by getting bigger, but this happens in a dysfunctional way and it doesn’t actually help the heart pump more blood.”
But he says that, in animals with heart failure, they found that CT1 caused the heart muscles to “grow in a more healthy way,” and it also stimulated the heart to grow new blood vessels. “This actually increases the heart’s ability to pump blood, just like what you would see with exercise and pregnancy,” he adds.
Prof. Megeney and team investigated the effects of CT1 in laboratory-grown heart muscle cells, rats, and mice. They also compared the effects of CT1 with those of phenylephrine (PE), which is a drug that stimulates the “bad kind of heart growth,” such as the harmful, irreversible enlargement that occurs in heart failure.
The researchers found that, when treated with CT1, heart muscle cells grow into longer, healthier fibers, whereas treatment with PE just results in wider growth. Also, with CT1, the new heart muscle tissue formed with new blood vessels alongside, which helps the heart to pump better. PE did not have this effect.
Furthermore, the heart growth that occurs with CT1 is reversible; when treatment stops, the organ returns to its original size, as it does when exercise stops or after pregnancy. The unhealthy heart growth that results from PE, on the other hand, is irreversible; when treatment stops, the heart remains dysfunctionally enlarged.
In two animal models of heart failure – one caused by heart attack, which damages the left side of the heart, and the other caused by pulmonary hypertension, or high blood pressure in the lungs, which damages the right side – CT1 treatment led to “dramatic improvements” in heart function.
Finally, although both CT1 and PE use the “cell suicide,” or apotosis, molecular pathway to trigger heart muscle growth, CT1 showed superior ability to control the pathway.
The team is excited by these findings because, if they translate to humans, they could vastly improve the prognosis for patients with heart failure.
Co-senior author Prof. Duncan Stewart – cardiologist, senior scientist, and executive vice president of research at the Ottawa Hospital – explains that, at present, the “only treatment for right heart failure is a transplant.”
“And although we have drugs that can reduce the symptoms of left heart failure,” he adds, “we can’t fix the problem, and left heart failure often leads to right heart failure over time.”
The researchers are hopeful that CT1 will work in humans with heart failure because it did so in several animal models of the condition.
They also point out that, while in theory, exercise is an obvious way to reap the benefits that CT1 appears to offer, this route is not open to people with heart failure, who can only exercise in a limited way.
Profs. Megeney and Stewart already have patents pending for using CT1 to treat heart problems, and they hope to partner with others to test the protein in human patients.
Nevertheless, they say that it will be several years, even if the tests are successful, before the treatment is ready for widespread clinical use.
“This experimental therapy is very exciting, particularly because it shows promise in treating both left and right heart failure.”
Prof. Duncan Stewart