Hydrogen sulfide improves ox-LDL-induced expression levels of Lp-PLA(2) in THP-1 monocytes via the p38MAPK pathway

Hydrogen sulfide (H(2)S) exerts an anti-atherosclerotic effect and decreases foam cell formation. Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) is a key factor involved in foam cell formation. However, the association between H(2)S and Lp-PLA(2) expression levels with respect to foam cell formation has not yet been elucidated. The present study investigated whether H(2)S can affect foam cell formation and potential signalling pathways via regulation of the expression and activity of Lp-PLA(2). 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-PLA(2), it also downregulates the expression level and activity of Cystathionine γ lyase. Exogenous supplementation of H(2)S decreased the expression and activity of Lp-PLA(2) induced by ox-LDL. Moreover, ox-LDL induced the expression level and activity of Lp-PLA(2) via activation of the p38MAPK signalling pathway. H(2)S blocked the expression levels and activity of Lp-PLA(2) induced by ox-LDL via inhibition of the p38MAPK signalling pathway. Furthermore, H(2)S inhibited Lp-PLA(2) 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 H(2)S inhibited ox-LDL-induced Lp-PLA(2) 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 H(2)S intervention in the progression of atherosclerosis.