oa Editorial (Thematic Issue: Endothelial Dysfunction: Treatment with Thiols)

In 2003 Wang described for the first time the properties of the H2S as a gasotransmitter. It is now well established that H2S exerts beneficial effect on the cardiovascular system including cardioprotection, regulation of the blood pressure and overall antioxidant effects on heart and vessels. In this issue Altaany reviews recent literature about H2S and endothelial dysfunction focusing on the interplay with nitric oxide, the most renown of three gasotransmitters. Endogenous H2S is produced by at least two enzymes involved in the metabolism of cysteine. In his contribution, Pushpakumar describes how hyperhomocysteinemia is related with increased risk for vascular disease based on endothelial dysfunction and emphasizing on the physiological role of H2S as a protective agent. It is known that the endothelial cells in physiological conditions account for the reduced glutathione pool and this molecule reacts with NO activating soluble guanylate cyclase. Bioavailability of reduced compounds, such as sulfur bound hydrogen, represents a redox-state balancing buffer. Depletion of such a buffer leads to a shift toward an oxidative intracellular environment. One of the inevitable effects of this pro-oxidative mechanism is aging. Along with aging, several pathological conditions (i.e. inflammation, obesity, diabetes mellitus, metabolic syndrome, etc.) contribute to the impaired ability of hydrogen to maintain the normal redox state. As suggested by the contributions of Masha and Park, thiols administration is able to restore the hydrogen capacity of modulating ox-reductive balance and to partially reverse the above mentioned pathological conditions. This effect is peculiar of thiols that are the only antioxidant able to reverse the endothelial dysfunction after the onset of the pathology while other antioxidants are effective only in primary prevention. The current issue, with different contribution, points to the opportunity to establish clinical trials based on the administration of thiols for the treatment of endothelial dysfunction.