Hydrogen sulfide ameliorates endothelial dysfunction in aging arteries by regulating ferroptosis

Area of Science:

• Cardiovascular Biology
• Aging Research
• Endothelial Function

Background:

• Aging is associated with vascular endothelial dysfunction, a key factor in cardiovascular diseases.
• Reduced endogenous hydrogen sulfide (H2S) levels and increased oxidative stress contribute to vascular aging.
• Ferroptosis, a regulated form of cell death, has been implicated in endothelial dysfunction.

Purpose of the Study:

• To investigate the mechanisms underlying age-related vascular endothelial dysfunction.
• To determine the role of endogenous H2S production and ferroptosis in renal artery aging.
• To evaluate the therapeutic potential of H2S in ameliorating endothelial dysfunction in aging.

Main Methods:

• Analysis of plasma and renal artery tissues from elderly patients and age-matched controls.
• Utilized animal models (SD rats) to study H2S and ferroptosis in renal arteries.
• Experimental interventions included administration of NaHS, Ferrostatin-1 (ferroptosis inhibitor), and erastin (ferroptosis inducer).

Main Results:

• Elderly individuals exhibited downregulated cystathione-γ-lyase (CSE) protein expression, reduced plasma H2S, elevated lipid peroxidation, and iron accumulation, leading to ferroptosis and impaired renal artery endothelial function.
• H2S supplementation enhanced CSE expression, boosted endogenous H2S production, decreased lipid peroxidation, and inhibited ferroptosis, thereby improving vascular endothelial function in the elderly group and animal models.
• NaHS treatment, Ferrostatin-1, and erastin modulated ferroptosis-related proteins, with NaHS and Ferrostatin-1 inhibiting ferroptosis and improving endothelial function.

Conclusions:

• Endothelial dysfunction in aging is closely linked to diminished endogenous H2S levels and ferroptosis in vascular endothelial cells.
• H2S plays a protective role by reducing lipid peroxidation and inhibiting ferroptosis, consequently improving endothelial function in aged vasculature.
• Targeting H2S pathways and ferroptosis presents a promising therapeutic strategy for age-related vascular endothelial dysfunction.