Atherosclerosis and the Hydrogen Sulfide Signaling Pathway – Therapeutic Approaches to Disease Prevention

Abstract

Hydrogen sulfide (H₂S) is now admitted as a third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO), albeit it was originally considered as a foul and poisonous gas. Endogenous H₂S production in mammalian cells is counting on the three enzymes acting on cysteine. Involvement of H₂S in various physiological and pathological processes has been extensively studied in the last fifteen years. Mounting evidence suggests that H₂S is able to protect against atherosclerosis development and progression. Exogenous H₂S supplement has salutary effects on atherogenesis, and reduction of the endogenous H₂S level accelerates atherosclerosis. The anti-atherosclerotic mechanisms of H₂S have been descried in different aspects, including endothelium preservation, antioxidative action, anti-inflammatory responses, vasorelaxation, regulation of ion channels, etc. However, further investigation is still needed to help us gain more insights into the fundamental underlying mechanisms, and that will allow us to design better therapeutic applications of H₂S in the treatment of atherosclerosis.

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

“…The anti-atherosclerotic mechanisms of H 2 S have been gradually described, including anti-inflammatory response, anti-oxidative action, endothelial function preservation, inhibition of foam cell formation and regulation of ion channels (Altaany et al, 2014;Mani et al, 2014;Xu et al, 2014;Wang et al, 2017;Barton and Meyer, 2019). Reduced CSE expressions at both mRNA and protein levels are detected in ox-LDL-treated endothelial cells and in aortas from apolipoprotein E knockout (ApoE -/-) mice (Leucker et al, 2017).…”

Hydrogen sulfide and vascular regulation – An update

“… [96] also demonstrated that decreased endogenous H 2 S generation accelerated AS in CSE-knockout mice. Accumulating evidence [97] , [98] has shown that endogenous H 2 S produced by CSE in blood vessels has an anti-AS effect. Unstable plaques generated by AS are prone to rupture and have the risk of infarction [99] .…”

Perivascular adipose tissue in cardiovascular diseases – an update

“…This observation is also supported by a study on the ApoE −/− mice consuming high-fat diet, showing that H 2 S may inhibit the atheromatous lesions progression, by regulating the expression of CX3CR1 and C-X3-C CX3CL1, in atheromatous plaques macrophages. However, the H 2 S antiatheromatous action may involve several mechanisms, such as vasorelaxation, endothelium preservation, anti-inflammatory responses, and the regulation of ion channels or antioxidative action (33), so further research is necessary to ensure validation.…”