Trimethylamine oxide and its possible role in the development and progression of cardiovascular disease

Abstract

Cardiovascular diseases continue to be the leading cause of death throughout the world and in Russia. Therefore, new possible risk factors for their development and progression are being studied. To date, information have been accumulated on unfavorable prognostic effect of elevated trimethylamine oxide (TMAO) levels on cardiovascular events, and the possible role of phospholipids (PLs) is being discussed. The aim of this review was to analyze the literature data on the potential relationship of TMAO and PLs with cardiovascular risk (CVR), as well as possible solutions to this problem. The search and analysis of publications was performed using Elibrary, PubMed, Medline, and Google Scholar databases in the period from their creation to 2021. It was found that high TMAO concentrations can have pro-inflammatory effects, stimulate atherogenesis and increase platelet aggregation. An increase in the blood TMAO levels increases the risk of cardiovascular events in patients with coronary artery disease, is associated with an increased risk of cardiovascular and all-cause death in patients with peripheral arterial disease and heart failure, and correlates with the extent of brain regions involved in stroke. The most important part in TMAO formation is taken by the gut microbiota, which metabolizes substrates, including PLs, to trimethylamine, which, when absorbed, is converted into TMAO in the liver. The analysis of available studies shows that the excessive intake of PLs into the gastrointestinal tract and the increased TMAO production are potentially interrelated with an increase in CVR. At the same time, PLs are currently used as drugs, in particular, as hepatoprotective agents. In view of this, large-scale randomized clinical trials are needed to study the CVR profile in patients receiving such therapy. Currently, other hepatoprotective agents are available that are devoid of such potential risks, since they do not contain PLs. One of these agents is ursodeoxycholic acid, which has proven its effectiveness and safety, including in patients with high CVR in routine clinical practice.

Atherosclerosis and trimethylamine-N-oxide — the gut microbiota potential

“…Существующие методы антиатеросклеротической терапии не всегда помогают достигать целевых метаболических показателей и при этом сопряжены со значительными побочными эффектами [3]. Потому в последние десятилетия внимание исследователей привлекает микробная теория развития атеросклероза [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Цель обзора -проанализировать данные о потенциальной роли метаболита кишечной микробиоты триметиламин-N-оксида (ТМАО) в патогенезе атеросклероза и новые терапевтические подходы для снижения циркулирующего ТМАО.…”

“…Обычно повышенный уровень ТМАО в сыворотке крови связывают с возрастающим риском ССЗ, но к настоящему времени описан широкий диапазон эффектов ТМАО. Так, ТМАО действует как осмолит, который позволяет адаптироваться к изменениям солености и гидростатического давления [25], обеспечивает стабильность структуры белков и нуклеиновых кислот [8], обладает иммунотропным действием [27] и другими свойствами, что некоторыми авторами расценивается как благоприятное действие ТМАО [28]. ТМАО в основном выводится из кровотока почками, поэтому функцию почек также важно учитывать при оценке уровня ТМАО в системном кровотоке [12].…”