Hydrogen sulfide improves ox‑LDL‑induced expression levels of Lp‑PLA2 in THP‑1 monocytes via the p38MAPK pathway

Abstract

Hydrogen sulfide (H2S) exerts an anti-atherosclerotic effect and decreases foam cell formation. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a key factor involved in foam cell formation. However, the association between H2S and Lp-PLA2 expression levels with respect to foam cell formation has not yet been elucidated. The present study investigated whether H2S can affect foam cell formation and potential signalling pathways via regulation of the expression and activity of Lp-PLA2. Using human monocytic THP-1 cells as a model system, it was observed that oxidized low-density lipoprotein (ox-LDL) not only upregulates the expression level and activity of Lp-PLA2, it also downregu-lates the expression level and activity of Cystathionine γ lyase. Exogenous supplementation of H2S decreased the expression and activity of Lp-PLA2 induced by ox-LDL. Moreover, ox-LDL induced the expression level and activity of Lp-PLA2 via activation of the p38MAPK signalling pathway. H2S blocked the expression levels and activity of Lp-PLA2 induced by ox-LDL via inhibition of the p38MAPK signalling pathway. Furthermore, H2S inhibited Lp-PLA2 activity by blocking the p38MAPK signaling pathway and significantly decreased lipid accumulation in ox-LDL-induced macrophages, as detected by Oil Red O staining. The results of the present study indicated that H2S inhibited ox-LDL-induced Lp-PLA2 expression levels and activity by blocking the p38MAPK signalling pathway, thereby improving foam cell formation. These findings may provide novel insights into the role of H2S intervention in the progression of atherosclerosis.