Modulation of Endothelial Function by TMAO, a Gut Microbiota-Derived Metabolite

Abstract

Endothelial function is essential in the maintenance of systemic homeostasis, whose modulation strictly depends on the proper activity of tissue-specific angiocrine factors on the physiopathological mechanisms acting at both single and multi-organ levels. Several angiocrine factors take part in the vascular function itself by modulating vascular tone, inflammatory response, and thrombotic state. Recent evidence has outlined a strong relationship between endothelial factors and gut microbiota-derived molecules. In particular, the direct involvement of trimethylamine N-oxide (TMAO) in the development of endothelial dysfunction and its derived pathological outcomes, such as atherosclerosis, has come to light. Indeed, the role of TMAO in the modulation of factors strictly related to the development of endothelial dysfunction, such as nitric oxide, adhesion molecules (ICAM-1, VCAM-1, and selectins), and IL-6, has been widely accepted. The aim of this review is to present the latest studies that describe a direct role of TMAO in the modulation of angiocrine factors primarily involved in the development of vascular pathologies.

Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial Cells

“…Endothelial cells are involved in numerous physiological and pathological processes [5,[10][11][12]48] and Ang II is a crucial player in the physiology and physiopathology of the endothelium [13,[17][18][19].…”

“…[11,12]. Endothelial functions are governed by numerous factors such as lifestyle, behavioral factors, gut microbiota, sympathetic and immune activation, sexual and vasoactive hormones such as the renin-angiotensin-aldosterone system (RAAS) [13][14][15][16]. Preclinical and clinical studies support the hypothesis that RAAS mainly contributes to the pathogenesis of some CVDs.…”

Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder

“…Additionally, proinflammatory monocytes and elevated TMAO levels were substantially associated in stroke patients. According to Haghikia et al (165) higher cardiovascular events such as myocardial infarction, recurrent stroke, and cardiovascular death were also linked to a raised TMAO plasma level. Numerous human investigations have also supported the involvement of TMAO in CVD.…”