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Vasoprotective properties of peptides IN VITRO
Cardiovascular pathology is a frequent disease associated with higher death rates among the elderly. According to the World Health Organisation, coronary heart disease, stroke and high blood pressure are the major killers.
The problem is aggravated by the fact that cardiovascular diseases commonly occur during the early stages when they are difficult to treat. This leads to large numbers of disabilities and need for long-term rehabilitation after stroke.
Thus, high prevalence and low efficiency of primary and secondary prevention determines the relevance and increasing interest in studying cardiovascular diseases.
Our new lecture as a part of Scientific Information Centre - Vasoprotective Properties Of Peptides In Vitro - focuses on this topic.
The lecture reviews the molecular mechanisms of vascular cell aging and the possibilities of regulation of this process by vasoprotective peptides, which opens new perspectives for the development of vasoprotective and geroprotective preparations. One such vasoprotective peptide is Vesugen, which normalizes the expression of signaling molecules, restores intercellular contacts and increases the expression of proteins involved in cell regeneration.
The scientific lecture is prepared by Ekaterina Mironova, Ph.D.:
- a senior research fellow of the laboratory for Molecular Mechanisms of Ageing from the Department of biogerontology of Saint-Petersburg Institute of bioregulation and gerontology
- a senior research fellow of the Molecular Biomedicine Center - Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation
Let’s take care of our health together, this is our primary and most precious resource!
Read the presentation - Vasoprotective properties of peptides IN VITRO
Vasoprotective properties of peptides IN VITRO
Ekaterina S. Mironova, Ph.D.
Cardiovascular pathology (CVD) is one of the most common diseases with a high mortality risk in elderly and senile people. The main causes of death are ischemic heart disease and atherosclerosis. According to statistics from the World Health Organization, myocardial infarction is the cause of death in more than 30% of cases. In Russia, CVD accounts for approximately 55% of the causes of total mortality. To date, there is a trend towards a decrease in the average age of CVD manifestation. A feature of the course of CVD in the elderly is a combination of pathology of various body systems, which leads to the use of various pharmaceuticals.
Existing drugs used in the treatment of CVD in people of older age groups have limitations due to side effects: they can cause dysfunction of the gastrointestinal tract, increased synthesis of liver enzymes, clouding of the lens, disorders in the hematopoietic system, mental disorders, myopathy.
In this regard, the search for new effective and safe treatments for CVD is particularly relevant. The study of the vascular cells aging molecular mechanisms and the possibility of regulating this process with the help of vasoprotective peptides opens up new prospects for the development of vaso- and geroprotective drugs with high efficiency and the absence of side effects aimed at the treatment of CVD [Khavinson, 2020].
From the polypeptide complex Ventfort®, which was isolated from the vessels of young animals, the tripeptide Vesugen® (KED, Lys-Glu-Asp) was synthesized. It was found that this tripeptide has a wide spectrum of action in various experimental models.
The effect of the Vesugen® peptide on the signaling molecules expression in vascular human embryo endothelial cells in vitro was studied in normal conditions, with atherosclerosis and restenosis. Vesugen® peptide was found to normalize the increased expression of Endothelin-1 in atherosclerosis. In addition, Vesugen® restores intercellular contacts of endotheliocytes carried out by Cx-37, increasing the expression of this connexin. Also, the geroprotective effect of the Vesugen® peptide on the endothelium is realized in an increasing of Sirt-1 expression, a protein involved in DNA repair [Kozlov, 2016].
In organotypic cell cultures obtained from young and old animals, and in dissociated cultures of vascular endotheliocytes during their aging, Vesugen® stimulated the proliferative protein Ki-67 synthesis, the expression of which decreased during cell aging. Molecular docking methods revealed the possibility of Vesugen® binding to the MKI67 gene promoter regions (gene of Ki-67 protein). CATC binding site was found. Thus, the vasoprotective effect of Vesugen® can be realized through epigenetic regulation of the expression of the gene encoding the proliferative protein Ki-67 [Khavinson, 2014].
During aging of the vascular endothelium in human cell cultures, Vesugen® reduced the expression level of p53, a protein responsible for apoptosis, the expression of which increases during cell aging. Expression of connexin Cx43 and vascular endothelial growth factor VEGF practically don’t during aging of human and animal vascular cells. Nevertheless, Vesugen® increased the expression of Cx43 and VEGF in cultures of human and rat vessels during aging.
Effect of Vesugen® on the expression of Endothelin-1, Sirt-1, Cx37, -43, Ki67, p53, VEGF proteins in cultures of human and animal endothelial cells during their aging play an important role in understanding the molecular mechanisms of this peptide action on the the cardiovascular system function. Thus, the vasoprotective effect of Vesugen® is carried out by regulating the processes of cell renewal, reducing the level of apoptosis and stimulating intercellular interactions.
