Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function

Abstract

Cardiovascular functionality strictly depends on endothelial cell trophism and proper biochemical function. Any condition (environmental, pharmacological/toxicological, physical, or neuro-humoral) that changes the vascular endothelium has great consequences for the organism's wellness and on the outcome and evolution of severe cardiovascular pathologies. Thus, knowledge of the mechanisms, both endogenous and external, that affect endothelial dysfunction is pivotal to preventing and treating these disorders. In recent decades, significant attention has been focused on gut microbiota and how these symbiotic microorganisms can influence host health and disease development. Indeed, dysbiosis has been reported to be at the base of a range of different pathologies, including pathologies of the cardiovascular system. The study of the mechanism underlying this relationship has led to the identification of a series of metabolites (released by gut bacteria) that exert different effects on all the components of the vascular system, and in particular on endothelial cells. The imbalance of factors promoting or blunting endothelial cell viability and function and angiogenesis seems to be a potential target for the development of new therapeutic interventions. This review highlights the circulating factors identified to date, either directly produced by gut microbes or resulting from the metabolism of diet derivatives as polyphenols.

Keywords: cardiovascular diseases; endothelial cell; endothelial dysfunction; gut microbiota; hypertension; inflammation; metabolite; nitric oxide; polyphenols; reactive oxygen species.

Figure 1

Features and functions of a healthy endothelium (left panel) and dysfunctional endothelium (right panel). The evolution from functional to dysfunctional endothelial cells (ECs) depends on various factors both exogenously (pollutants, toxins, drugs, diet components) and endogenously produced (oxidized lipoproteins: ox-LDL, hyperglycemia and glycation products: AGE, misfolded proteins such as beta-amyloid-Aβ, reactive oxygen species: ROS). Here, we have focused on the hypothesis that microbiota derived metabolites can influence endothelial behavior and thus cardiovascular disease (CVD) risk and manifestation.

Figure 2

Schematic representation of the activity of circulating metabolites originating from the gut microbiota (GM) on endothelial cell function. Alteration of endothelial viability and metabolism in its turn influences the outcome of hypertension, atherosclerosis, and other CVDs, and the type and extent of the angiogenic response.