Implications of Hydrogen Sulfide in Development of Pulmonary Hypertension

The pathological mechanisms underlying pulmonary hypertension (PH), as well as its treatment strategy, are crucial issues in this field. This review aimed to summarize the pathological mechanisms by which the hydrogen sulfide (H₂S) pathway contributes to PH development and its future implications. The data in this review were obtained from Medline and PubMed sources up to 2022 using the search terms "hydrogen sulfide" and "pulmonary hypertension". In the review, we discussed the significance of endogenous H₂S pathway alteration in PH development and showed the advance of the role of H₂S as the third gasotransmitter in the mechanisms for hypoxic PH, monocrotaline-induced PH, high blood flow-induced PH, and congenital heart disease-associated PH. Notably, H₂S plays a crucial role in the development of PH via certain mechanisms, such as inhibiting the proliferation of pulmonary artery smooth muscle cells, suppressing the inflammation and oxidative stress of pulmonary artery endothelial cells, inducing pulmonary artery smooth muscle cell apoptosis, and interacting with other gaseous signaling pathways. Recently, a variety of H₂S donors were developed, including naturally occurring donors and synthetic H₂S donors. Therefore, understanding the role of H₂S in PH development may help in further exploring novel potential therapeutic targets of PH.