Growth factors against heart attack
Vascular growth genes will help to recover after a heart attack
The staff of the Russian National Medical Research Center of Cardiology evaluated the effectiveness of an experimental method of gene therapy for model organisms – rats – with an analogue of myocardial infarction. It turned out that the introduction of variants of the vascular endothelial growth factor VEGF165 and hepatocyte growth factor HGF genes reduces the severity of the consequences of infarction in laboratory animals. Moreover, they work more efficiently together than separately. A scientific article with the results of the study was published in the journal PLOS ONE (Makarevich et al., Angiogenic and pleiotropic effects of VEGF165 and HGF combined gene therapy in a rat model of myocardial infarction).
New methods of gene therapy for various diseases have been developed very intensively in recent years. At the end of August 2017, the first of them received approval from the FDA, an American organization that deals with food and drug quality control. Since then, several more officially approved "gene drugs" have appeared, and many are undergoing clinical (in humans) and preclinical (in animals) studies.
One of the directions of development of gene therapy is to enhance the growth of blood vessels feeding the heart after myocardial infarction. A heart attack is an acute violation of the blood supply to an organ or part of it, in the case of the myocardium – part of the heart muscle. For a number of reasons, the vessels that feed the heart (they are called coronary) stop bringing blood to this organ, which is why the myocardium does not receive enough nutrition, loses the ability to contract normally, and some of its cells die. In their place, a scar is formed, consisting mainly of collagen protein.
In order for the smallest possible volume of the heart muscle to suffer from a heart attack, it is necessary to restore its blood supply as quickly as possible. This can theoretically be done by "growing" new coronary vessels. Several genes are responsible for their growth rate, including the gene for vascular endothelial growth factor VEGF165 and the gene for hepatocyte growth factor HGF (although its name indicates liver cells, it also participates in the formation of the endothelium – the inner lining of blood vessels). Accordingly, "improved" variants of VEGF165 or HGF can be introduced into the heart area.
Such experiments have already been conducted on laboratory animals. However, it is likely that together these genes will work more efficiently. This was verified by Russian scientists in their study. They used adult male rats that had their coronary artery bandaged– the main vessel that brings blood to the heart muscle cells. After ligation of a quarter of rodents, plasmids (small ring DNA molecules capable of embedding into other DNA) containing only VEGF165 were injected along the edges of the damaged area of the heart, another quarter – plasmids with HGF, the third – plasmids containing both genes. The rats from the control group were not given gene therapy: they got an "empty" plasmid.
After a while, long enough for all wounds to heal, the animals were euthanized, and the tissue of their hearts was cut into ultrathin slices. Using various microscopy methods, the authors determined how many cells died in the infarction zone, how much collagen is contained in the heart (i.e., what size scars were formed), what is the density of working blood vessels there, as well as how intensively cardiomyocyte precursors were formed in the studied area – that is, how much heart tissue was capable of recovery.
All three types of gene therapy (injection of one VEGF165, injection of one HGF, injection of VEGF165 and HGF simultaneously) proved to be effective. In each case, thanks to the introduction of plasmids, it was possible to increase the number of capillaries and precursors of cardiomyocytes and reduce the area of lesion and the number of dead myocardial cells compared with the control group. However, the therapeutic effect was most pronounced on the organs of those animals that were injected with plasmids of two types at once – with VEGF165 and with HGF.
Thus, it is possible to reduce the severity of the consequences of myocardial infarction for the heart thanks to gene therapy – the introduction of genes encoding proteins to activate the growth of blood vessels. But it should be borne in mind that each gene is able to influence several processes at once.
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