TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide

Area of Science:

• Vascular Biology
• Mitochondrial Medicine
• Biochemistry

Background:

• Endothelial dysfunction contributes to cardiovascular diseases.
• Hydrogen sulfide (H2S) exhibits vasoprotective properties via anti-inflammatory and redox regulation.
• Reduced H2S bioavailability is linked to chronic conditions like cardiovascular disease, diabetes, atherosclerosis, and preeclampsia.

Purpose of the Study:

• To investigate the protective effects of H2S on endothelial cells, focusing on mitochondrial health and apoptosis.
• To elucidate the mechanisms by which H2S rescues endothelial cells from apoptosis.
• To explore the role of H2S in maintaining endothelial function in the context of oxidative stress.

Main Methods:

• Induction of endothelial dysfunction using TNF-α.
• Assessment of oxidative stress, apoptosis markers (cytochrome c release, caspase activation), and mitochondrial morphology.
• Treatment with a slow-releasing H2S donor (GYY4137) to evaluate its protective effects.
• Analysis of S-sulfhydration of pro-caspase 3 and mitochondrial network integrity.

Main Results:

• TNF-α induced endothelial oxidative stress, apoptosis via mitochondrial pathways, and altered mitochondrial morphology.
• Post-treatment with GYY4137 significantly reduced oxidative stress and caspase activity.
• GYY4137 prevented TNF-α-induced endothelial apoptosis and improved mitochondrial health.
• Exogenous H2S enhanced S-sulfhydration of pro-caspase 3, indicating a direct molecular interaction.

Conclusions:

• H2S exerts cytoprotective effects on endothelial cells through a mitochondrial-dependent pathway.
• The gasotransmitter H2S preserves mitochondrial integrity and function during stress.
• Modulating H2S bioavailability may represent a therapeutic strategy for endothelial dysfunction and associated cardiovascular complications.