Protective Role of H2S in High Glucose-Induced Cardiomyocyte and Endothelial Cell Dysfunction: A Mechanistic Review.

Hydrogen sulfide (H₂S), recognized as a significant gasotransmitter, has been shown to effectively reduce damage to cardiomyocytes and endothelial cells caused by diabetes. Its protective effects primarily stem from several mechanisms, including S-sulfhydration of proteins, reduction of cell death, alleviation of mitochondrial damage, improvement of ion channel dysfunction, interaction with nitric oxide, and modulation of angiogenesis. H₂S is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), whose expression is significantly reduced under diabetic conditions, including experimental high-glucose treatment in cells and diabetes mellitus animal models. This review summarizes the protective role of H₂S and its donors in these pathological processes, highlights existing research gaps-including challenges in the targeted delivery of H₂S donors, limited clinical translation, and incomplete mechanistic understanding-and discusses future directions for developing targeted H₂S-based therapeutic strategies.