MADRID, 29 Abr. (EUROPA PRESS) –
After a heart attack the functioning of the heart is not the same but it could be again and have a healthy heart again thanks to a new discovery that allows the clock to be turned back using RNA to instruct cells in an injured heart to eliminate the scar tissue and recreate heart muscle, allowing the heart to function like new.
The study, conducted in mice by the American Society for Biochemistry and Molecular Biology and published in the Journal of Biological Chemistry, shows that it is possible to recover almost all of the heart function that was lost after a heart attack by reversing the aging of the fibroblasts in the heart.
“Adult human hearts aren’t very good at repairing themselves. Once they have a heart attack or any kind of damage, there’s no ability to replace the dying heart muscle. So what the heart does to prevent It basically explodes is that it activates the fibroblasts to go in and form a scar,” explains Conrad Hodgkinson, associate professor of medicine and pathology at Duke University School of Medicine, who supervised the study.
Like the scars on the skin that result from injury or surgery, the scar tissue that develops in the heart after a heart attack “is hard and inflexible and can prevent the organ from functioning to its full potential.” adds Hodgkinson.
Hodgkinson and his team wanted to find an efficient way to convert scar tissue back into functional heart muscle to essentially reverse the effects of a heart attack. To do this, they set out to find a way to transform fibroblasts, a type of cell that contributes to the formation of connective tissue, into heart muscle cells through a process called cellular reprogramming.
Hodgkinson’s lab delivered reprogramming instructions to cells in the form of RNA. However, they found that adult fibroblasts are not very good at following instructions and are resistant to reprogramming.
“We found that if you take cardiac fibroblasts from juveniles, they reprogram themselves very well,” says Hodgkinson. “But if you take adult cardiac fibroblasts, in fact, they don’t respond at all. So we tried to understand whether the aging process really interfered with fibroblast reprogramming.”
The researchers found that an oxygen-sensing protein, Epas1, prevents adult fibroblasts from reprogramming. They were able to harness the regenerative capacity of young cells by blocking Epas1 in adult fibroblasts.
“When we reversed the aging process of the fibroblasts, essentially making the fibroblasts think they were young again, we turned more fibroblasts into heart muscle,” Hodgkinson explains.
The researchers formulated a cocktail of RNA and packaged it into exosomes, a natural product produced by most cells. This technology allowed them to deliver the exosomes without surgical interventions. Exosome bundles have unique properties that guide them to cardiac fibroblasts within an injured heart.
When the researchers used the RNA-filled exosomes to instruct fibroblasts to reprogram themselves in a mouse that had just suffered a heart attack, the results were, according to Hodgkinson, “impressive.”
Cellular reprogramming, along with reversing cellular aging, has limitless future applications, including restoring loss of neurons in the brains of dementia patients and removing skin scarring in psoriasis patients without invasive surgical interventions, he said. Hodgkinson.
