H₂S signaling and extracellular matrix remodeling in cardiovascular diseases: A tale of tense relationship

Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network that not only provides mechanical support but also transduces essential molecular signals in organ functions. ECM is constantly remodeled to control tissue homeostasis, responsible for cell adhesion, cell migration, cell-to-cell communication, and cell differentiation, etc. The dysregulation of ECM components contributes to various diseases, including cardiovascular diseases, fibrosis, cancer, and neurodegenerative diseases, etc. Aberrant ECM remodeling is initiated by various stress, such as oxidative stress, inflammation, ischemia, and mechanical stress, etc. Hydrogen sulfide (H₂S) is a gasotransmitter that exhibits a wide variety of cytoprotective and physiological functions through its anti-oxidative and anti-inflammatory actions. Amounting research shows that H₂S can attenuate aberrant ECM remodeling. In this review, we discussed the implications and mechanisms of H₂S in the regulation of ECM remodeling in cardiovascular diseases, and highlighted the potential of H₂S in the prevention and treatment of cardiovascular diseases through attenuating adverse ECM remodeling.