The Role of H2S in Atherosclerosis and Associated Cardiometabolic Comorbidities

Hydrogen sulfide (H₂S) is an important gasotransmitter with multiple roles and is involved in several pathophysiological processes, including atherosclerosis and associated cardiometabolic comorbidities. This chapter examines the molecular mechanisms by which H₂S can influence the development and progression of atherosclerosis, including its effects on vascular tone, angiogenesis, oxidative stress, and inflammation, which can also affect atherosclerotic plaque stability. Moreover, we describe how H₂S affects the outcomes of cardiometabolic comorbidities associated with atherosclerosis, such as diabetes, hypertension, cardiac ischemia-reperfusion injury (IRI), stroke, metabolic-associated fatty liver disease (MAFLD), and kidney disease. Finally, we discuss how H₂S levels could potentially serve as biomarkers and the potential of increasing H₂S levels (both donors and metabolic pathway modulators) as promising therapeutic agents for improving vascular function, reducing plaque formation, and mitigating cardiovascular disease risk.