Gene therapy of a heart attack
Scientists from Russia have created a gene therapy for the treatment of heart attacks
Molecular biologists from Moscow State University and NMIC of Cardiology have created a gene therapy that restores the work of damaged areas of the heart after a heart attack, including two "life genes" in them. The first results of its testing on rats were presented in the journal PLoS One.
"We found that the gene therapy we developed activates heart stem cells – a reserve that the body can use to restore the myocardium after damage," says Pavel Makarevich from the Institute of Regenerative Medicine of Moscow State University, whose words are quoted by the press service of the university.
The human and animal heart is a unique organ whose cells can simultaneously spontaneously generate electrical impulses and contract, without requiring a constant flow of "commands" from the spinal cord or brain. Current pulses are produced by the so-called "driver cells", and cardiomyocytes are muscle cells that use them to reproduce contractions and relaxation at the right moments of time.
Disturbances in the work of "driver cells" and these contacts, as a rule, lead to the development of heart failure and other serious health problems. For this reason, as scientists note, the heart is only transplanted entirely today – scientists cannot yet replace the dead areas of the heart muscle that died after a heart attack using stem cell cultures or fragments of heart tissue.
Makarevich and his colleagues solved this problem by creating a special DNA molecule that can penetrate damaged heart muscle cells and restore their vital functions, simultaneously stimulating the growth of new vessels necessary for its supply of oxygen and nutrients.
Scientists have been trying for a long time, as the biologist notes, to use retroviruses and other types of gene therapy to "fix" the heart, but in fact all such experiments ended either in failure or with very modest success.
The reasons for this, as Makarevich and his team found out, was that the authors of such forms of gene therapy "targeted" only one of several genes associated with the regeneration of the heart muscle, and ignored the rest of the DNA, potentially necessary for the "repair" of the heart.
Guided by these considerations, geneticists from MSU and NMIC Cardiology created their own version of gene therapy, which included two very different genes, VEGF165 and HGF. The first section of DNA stimulates the growth of new vessels, and the second one causes stem cells to turn into new muscle fibers.
In addition to their main functions, these genes have an unusual effect on each other – HGF plays the role of a kind of "brake" VEGF165, reducing the growth rate and the number of new vessels. In most cases, this has a beneficial effect on the work of the body, since the appearance of an excessively large number of capillaries causes inflammation and very dangerous swelling.
Biologists tested the work of the combination of these genes on rats in which they artificially caused a heart attack by sewing up part of their coronary artery. When the heart tissue began to die, doctors introduced gene therapy into it and monitored changes in its vital activity.
As this experiment showed, both genes noticeably slowed down the death of both those and other myocardial cells, and after about two weeks, almost all traces of a heart attack completely disappeared from their heart tissue.
Figure from the article in PLoS One (areas of fibrosis are colored blue) – VM.
Due to this, the walls of the heart are not "overgrown" with connective tissue, which usually occurs with the development of ischemia, and have not become less flexible than in healthy rodents.
Makarevich and his team expect that their gene therapy will be used to treat patients who have suffered a myocardial infarction after all preclinical and clinical studies.
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