Modulation of hydrogen sulfide by vascular hypoxia

Abstract

Hydrogen sulfide (H₂S) has emerged as a key regulator of cardiovascular function. This gasotransmitter is produced in the vasculature and is involved in numerous processes that promote vascular homeostasis, including vasodilation and endothelial cell proliferation. Although H₂S plays a role under physiological conditions, it has become clear in recent years that hypoxia modulates the production and action of H₂S. Furthermore, there is growing evidence that H₂S is cytoprotective in the face of hypoxic insults. This review focuses on the synthesis and signaling of H₂S in hypoxic conditions in the vasculature, and highlights recent studies providing evidence that H₂S is a potential therapy for preventing tissue damage in hypoxic conditions.

Keywords: H2S; cystathionine γ-lyase; endothelium; vascular smooth muscle.

Figure 1

Effects of hypoxia on CSE expression in the vascular wall. Note: Hypoxia has been shown to decrease CSE expression but direct effects of hypoxia on CSE activity are less defined. Abbreviations: H₂S, hydrogen sulfide; CBS, cystathionine β-synthase; CSE, cystathionine γ-lyase; VSMC, vascular smooth muscle cell; EC, endothelial cell; HIF1α, hypoxia inducible factor 1α; miR-21, microRNA-21; Sp1, specific ity protein 1; Cys, cysteine.

Figure 2

Hydrogen sulfide signaling in the vascular wall. Notes: H₂S can activate multiple signaling pathways in both endothelial and smooth muscle cells. These pathways increase proliferation and protect from oxidative stress. Abbreviations: H₂S, hydrogen sulfide; CO, carbon monoxide; Cys, cysteine; CBS, cystathionine β-synthase; CSE, cystathionine γ-lyase; VEGFR2, vascular endothelial growth factor receptor 2; ROS, reactive oxygen species; VSMC, vascular smooth muscle cell; Mito, mitochondria; EC, endothelial cell; CaM, calmodulin; RyR, ryanodine receptor; SR, sarcoplasmic reticulum.