Medical intervention that enables the heart to repair or regenerate cells damaged following a heart attack could soon be a new strategy for treating heart diseases.
Researchers at the University of Houston in the United States have reported a first-of-its-kind technology that not only repairs heart muscle cells in mice but also regenerates them following a heart attack, or myocardial infarction as it is medically known.
Myocardial infarction is a medical emergency where your heart muscles begin to die because they are not getting enough blood flow. This is usually caused by a blockage in the arteries that supply blood to your heart. If blood flow is not restored quickly, a heart attack can cause permanent heart damage and possibly death.
Results from the Global Burden of Disease study by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in the US, found that Coronary heart disease (CHD) to be the leading cause of morbidity and mortality throughout the world. The most common form of CHD is the myocardial infarction.
It is estimated 82 percent of deaths in low- and middle-income countries are caused by CVD and that nearly 24 million will die from CVDs by 2030. According to medical analysts, the ground-breaking new finding by scientists at University of Houston has the potential to become a powerful clinical strategy for treating heart disease in humans. The new technology developed by the team of researchers uses synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors — proteins that control the conversion of DNA into RNA — to mouse hearts.
The researchers demonstrated — through experiments conducted in vitro tissue culture dishes of muscle cells isolated from mouse hearts — that two mutated transcription factors, Stemin and YAP5SA, work in tandem to increase the replication of cardiomyocytes, or heart muscle cells in mouse heart cells.
Stemin is responsible for turning on stem cell-like properties in cardiomyocytes. Meanwhile, YAP5SA works by promoting organ growth that causes the myocytes to replicate even more. The aim of the experiments was to dedifferentiate the cardiomyocyte into a more stem cell-like state so that they could then regenerate and proliferate.
The study showed that, at least in vitro, Stemin and YAP5SA could be coaxed to repair damaged mouse hearts. Most notably, myocyte nuclei replicated on average 15-fold in 24 hours following heart injections that delivered those transcription factors.
When both transcription factors were injected into infarcted adult mouse hearts, the results surprised the scientists. The researchers discovered that cardiac myocytes multiplied rapidly within a day, and that over the next month hearts were repaired to near normal cardiac pumping function with little scarring.
An added benefit of using synthetic mRNA, is that it disappears in a few days as opposed to gene therapies delivered to cells by viral vectors. The use of viral vectors also raises several biosafety concerns, as they cannot be easily stopped once they are initiated. On the other hand, mRNA-based delivery turns over quickly and disappears.
No one has been able to do this to this extent before, and even though the experiments were on mouse heart cells, the researchers behind the finding believe that it could become a possible treatment for human heart patients in the future.
The findings are especially important because less than 1 percent of adult cardiac muscle cells can regenerate. Most people die with most of the same cardiomyocytes they had in the first month of life. When there is a heart attack and heart muscle cells die, the contracting ability of the heart is lost.
The new discovery that heart muscle cells could be coaxed back to repair or regenerate the damaged heart cells could in future lead to major improvements in the treatment of heart diseases.