20 June 2022

RNA against infarction

RNA therapy will help restore the heart after a heart attack

Sergey Vasiliev, Naked Science

Scientists from the University of Houston have demonstrated a new approach to restoring heart muscle after a heart attack. To do this, the cells return to the stem state with the help of special RNA molecules, after which they regenerate damaged tissues independently.

Such therapy proved to be excellent in experiments with laboratory mice: a month after the model heart attack, the animals almost completely recovered. This is reported in two articles published in The Journal of Cardiovascular Aging.

Heart muscle cells (cardiomyocytes) recover extremely poorly after damage. As a rule, the case ends with the formation of a half-dead scarred tissue that is unable to contract. This leads to a weakening of heart functions and an increased risk of new heart attacks.

That is why scientists and doctors pay special attention to the restoration of heart muscle cells and actively try to stimulate such processes. One of the areas of work is the "reprogramming" of cells with their temporary return to the state of stem cells, actively dividing and growing.

Robert Schwartz and his colleagues from the University of Houston have identified a pair of proteins that play the role of transcription factors. Experiments with cardiomyocyte cell cultures in vitro have shown that by regulating the activity of certain genes, Stemin and YAP5SA stimulate cell division and growth. This work is devoted to the first of the articles published recently by scientists (Xiao et al., Mutant SRF and YAP synthetic modified mRNAs drive cardiomyocyte nuclear replication). The second describes the first experiments with Stemin and YAP5SA in vivo, on laboratory animals (Xiao et al., STEMIN and YAP5SA synthetic modified mRNAs regenerate and repair infarcted mouse hearts).

YAP5SA.jpg

Damaged areas of the heart in mice treated with an mRNA cocktail (right) were actively regenerated, whereas in animals of the control group (left) they almost did not recover.

To deliver protein factors to the body, the authors encoded them in the form of matrix RNA (mRNA) molecules. Such molecules can serve as instructions for ribosomes, triggering the synthesis of the corresponding proteins right inside the cell — recall that this approach is the basis of some successful Covid-19 vaccines (including the vaccine created by Moderna and Pfizer) and is being actively tested to create drugs for other viral diseases.

To deliver protein factors to the body, the authors encoded them in the form of matrix RNA (mRNA) molecules. Such molecules can serve as instructions for ribosomes, triggering the synthesis of the corresponding proteins right inside the cell — recall that this approach is the basis of some successful Covid-19 vaccines (including the vaccine created by Moderna and Pfizer) and is being actively tested to create drugs for other viral diseases.

Scientists synthesized the necessary mRNAs and injected them into the heart muscle of model mice after a "heart attack" — such animals undergo targeted manipulations that create corresponding heart lesions in them.

After a day, their cardiomyocytes were divided 15 times more actively than in mice that did not receive the experimental drug, and the restoration of damaged tissues was much faster. After a month, the functions of the heart were restored almost completely, without the formation of scar tissue.

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