Cardiovascular diseases: pathophysiological role of gut microbiota and new targets for treatment and prevention

Despite certain success achieved in therapy and prevention, cardiovascular diseases (CVD) continue to be the leading cause of death of the population worldwide. One of the main reasons for this is that the pathophysiological mechanisms of the development of atherosclerosis, a disease that underlies most clinical forms of CVD, have not been fully understood yet, and therapy based on well-known concepts of pathogenesis, including lipid, does not provide the desired results. In this regard, search and identification of new molecular targets and therapeutic approaches is an important objective of modern medical science. In this direction, a completely new metabolic pathway identified by researchers, that links lipid consumption, gut microbiota (GM) and development of atherosclerosis, deserves interest. Thus, for the first time it was shown that GM uses food choline, as well as carnitine (found in red meat) for synthesis of trimethylamine (TMA), which, in turn, is rapidly oxidized by liver flavin monooxidases (FMO) to trimethylamine oxide (TMAO), that causes the development of atherosclerosis. Mechanisms of proatherogenic effect of TMAO, which, taken together, involve stimulation of inflow and suppression of outflow of cholesterol from the cell, have also been established. Another pathway of GM influence on the development or progression of atherosclerosis, that links the presence of bacterial infection and the degree of atherosclerosis development, has also been identified. It is believed that in this case, bacterial liposaccharides (LPS) interact with low-density lipoproteins (LDL), as a result of which LDL turn into atherogenic oxidized LDL. The article discusses possible therapeutic strategies for prevention and treatment of coronary atherosclerosis associated with both decreased production of TMAO and elimination of TMA from the intestines, and regulation of microbial metabolism (inhibition of microbial enzymes that produce TMA), as well as change in the structure of GM towards increase in the proportion of microorganisms beneficial to the human body (unable to produce TMA).

gut microbiota, trimethylamine oxide (TMAO), bacterial translocation, atherosclerosis, coronary heart disease, chronic heart failure

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