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

Xiaoya Zhai,1,* Yefei Gao,1,* Haifei Lou,1 Liping Meng,1 Jiedong Zhou,2 Hui Lin,3 Fukang Xu1 1Department of Cardiology, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China; 2Cardiovascular Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China; 3Department of Cardiology, The Affiliated Lihuili Hospital of Ningbo University Health Science Center, Ningbo, Zhejiang, 315211, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Lin, Email [email protected] Fukang Xu, Email [email protected]: 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.Keywords: H2S, diabetic cardiomyopathy, diabetes-induced endothelial cell damage