Harnessing Gasotransmitters to Combat Age-Related Oxidative Stress in Smooth Muscle and Endothelial Cells

Age-related oxidative stress is a critical factor in vascular dysfunction, contributing to hypertension and atherosclerosis. Smooth muscle cells and endothelial cells are particularly susceptible to oxidative damage, which exacerbates vascular aging through cellular senescence, chronic inflammation, and arterial stiffness. Gasotransmitters-hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO)-are emerging as promising therapeutic agents for counteracting these processes. This review synthesizes findings from recent studies focusing on the mechanisms by which H2S, NO, and CO influence vascular smooth muscle and endothelial cell function. Therapeutic strategies involving exogenous gasotransmitter delivery systems and combination therapies were analyzed. H2S enhances mitochondrial bioenergetics, scavenges ROS, and activates antioxidant pathways. NO improves endothelial function, promotes vasodilation, and inhibits platelet aggregation. CO exhibits cytoprotective and anti-inflammatory effects by modulating heme oxygenase activity and ROS production. In preclinical studies, gasotransmitter-releasing molecules (e.g., NaHS, SNAP, CORMs) and targeted delivery systems show significant promise. Synergistic effects with lifestyle modifications and antioxidant therapies further enhance their therapeutic potential. In conclusion, gasotransmitters hold significant promise as therapeutic agents to combat age-related oxidative stress in vascular cells. Their multifaceted mechanisms and innovative delivery approaches make them potential candidates for treating vascular dysfunction and promoting healthy vascular aging. Further research is needed to translate these findings into clinical applications.