From methionine to sulfide: Exploring the diagnostic and therapeutic potential of sulfur-containing biomolecules in hypertension

Sulfur-containing amino acids are involved in the regulation of vascular activity and blood pressure. Clinically, a positive correlation was found between serum homocysteine levels and blood pressure. On the other hand, methionine and cysteine levels were reduced in hypertensive patients. Recently, the redox state of sulfur-containing amino acids has emerged as potential diagnostic marker of cardiovascular health. Metabolomic studies have revealed a shift in thiol/disulfide ratio toward oxidized forms and overproduction of thiyl radicals in hypertensive patients. Although accumulating evidence confirms that sulfur-containing amino acids are essential for the maintaining of redox homeostasis and blood pressure control, their hypotensive and antioxidant properties have been primarily demonstrated in animal studies. While several groups are developing new targeted and triggered sulfur-based donors, standardized pharmacological interventions for hypertensive patients are largely absent and pose a challenge for future research. In this review, we summarize recent studies that investigate the role of sulfur-containing amino acids and their redox-active metabolites, including glutathione and sulfide, in blood pressure control and the development of systemic hypertension.