Turning over provocateurs
Our immune T cells are the "fifth column" of atherosclerosis
Atherosclerosis is sometimes also called the "silent killer" – this common chronic disease is the main cause of diseases of the cardiovascular system. One of the factors of its development may be the malfunction of the immune system, when the inflammatory process in the arteries is provoked by immune cells. However, scientists have recently found out that some of these "provocateurs" can be used to fight the disease.
A visible sign of atherosclerosis are atherosclerotic plaques – dense, round or oval formations protruding above the surface of the inner lining of a blood vessel. As a result of pathological changes in the walls of blood vessels, their lumen becomes too small, and tissues and organs face a shortage of oxygen. It is not surprising that atherosclerosis plays a leading role in the development of coronary heart disease and stroke, peripheral artery disease.
When talking about the causes and mechanisms of atherosclerosis, specialists usually use the word "multifactorial". One of the culprits for the development of plaques is cholesterol, a fat–soluble substance related to steroids, which is contained in the cell membranes of animals and humans.
Cholesterol circulates in the blood in the form of protein-lipid complexes, including low-density lipoproteins (LDL), responsible for its transport into cells. These molecular complexes, undergoing peroxidation, can damage the vascular wall. And in this sense, the formation of atherosclerotic plaques is considered as a reaction to this damage. In fact, it is an analogue of a "patch" on the wound.
Stages of development of atherosclerosis and blockage of the vessel
An important protein component of LDL is the protein apolipoprotein B (APOB). Scientists from the USA have discovered that this protein can be attacked by some immune cells from an extensive pool of T-lymphocytes (T cells), which contributes to inflammation and the progression of atherosclerosis. Experiments on laboratory mice have shown that as atherosclerosis progresses, the number of APOB-reactive T cells in the blood increases and they become more aggressive.
The researchers isolated these specific T-cells from blood samples of eight women, among whom were those suffering from atherosclerosis and cardiovascular diseases. It should be added that there are very few such cells in the blood in principle: out of 12 thousand studied T-cells, there were slightly more than a hundred APOB-reactive.
When scientists analyzed the RNA sequences in these cells reflecting the "operational" protein profile, it turned out to be different. According to these data, APOB-reactive T cells resemble, on the one hand, regulatory T cells that normally control the immune response and the process of inflammation. On the other hand, they are similar to memory T cells, which store information about the antigen that caused the immune response for a long time, and this similarity was higher in women with cardiovascular pathology.
Article by Saigusa et al. Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease published in the journal Nature Cardiovascular Research.
What is the practical "exhaust" of this work? Perhaps in the future, the results obtained will help improve the accuracy of the diagnosis of cardiovascular diseases. In principle, it is also possible to create a vaccine drug directed against reactive T cells, which can prevent the development or progression of atherosclerosis.
In the meantime, the scientists' immediate plans are to confirm their findings in a larger study on humans, including men, who, by the way, are more likely to suffer from atherosclerosis than the "weaker sex".
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