Novel H₂S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway

As a gaseous mediator, hydrogen sulfide (H₂S) has many physiological effects and pathological effects in atherosclerosis. In recent years, many exogenous H₂S donors have been synthesized to study atherosclerosis diseases. In this study, proglumide-(5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) (P-A) was synthesized as a H₂S donor. The protective effect and mechanism of P-A on HUVEC that was injured by ox-LDL were detected. The HUEVCs were affected by 100 μmol/L P-A for 24 h; the release of H₂S was the largest. After 100 μmol/L P-A acted on HUVEC damage model for 12 h, the cell proliferation activity was the best. The results showed that P-A can downregulate the expression of p-NF-кBp65 protein and reduce the amount of TNF-α and IL-6 and promote the formation of IL-10 by inhibiting the NF-кB pathway, and also induce the expression of superoxide dismutase (SOD) to protect HUVEC from ox-LDL injury. P-A can also regulate JAK/STAT pathway to reduce the expression of p-JAK2 protein and reduce the production of IL-6 and TNF-α. P-A has protective effect on HUVEC injured by ox-LDL, and the protective mechanism is related to the regulation of JAK/STAT pathway and NF-кB pathway.