H2S signaling: the behind-the-scenes "mediator" in melatonin's defense against angiotensin II-disrupted smooth muscle cell functions

Abstract

Chronic activation of Angiotensin II (Ang II), a key peptide in the renin-angiotensin system (RAS), is associated with vascular remodeling and cardiac dysfunction. Hydrogen sulfide (H2S), a novel gasotransmitter, is recognized for its cardioprotective properties, particularly being attributed to its ability to counteract RAS activation. Cystathionine-γ-lyase (CSE) serves as the primary H2S-producing enzyme in the cardiovascular system. Along with H2S, accumulating evidence reveals that the rhythmicity of melatonin has a crucial role in a variety of cardiovascular pathophysiological processes via its anti-inflammatory, antioxidant, and anti-hypertensive functions. This study investigated the effects of Ang II and melatonin on the CSE/H2S system and further explored the mediation of H2S on the protective roles of melatonin against Ang II-disrupted smooth muscle cell (SMC) functions. Here, it was found that incubation of mouse vascular SMCs with melatonin induced H2S production, which effectively reversed Ang II-stimulated SMC proliferation, migration, and oxidative stress, possibly through blocking Ang II receptor 1. Taken together, this study suggests that targeting the CSE/H2S pathway via melatonin may represent a promising therapeutic strategy for preventing and treating cardiovascular diseases. Further studies are necessary to investigate the mechanisms underlying the stimulatory roles of melatonin on the CSE/H2S pathway and the involvement of melatonin/H2S in protecting against the detrimental effects of Ang II.