Hydrogen sulfide inhibits macrophage-derived foam cell formation

Recent evidence indicates that hydrogen sulfide (H2S) exerts an antiatherogenic effect, but the mechanism is unclear. Formation of macrophage-derived foam cells is a crucial event in the development of atherosclerosis. Thus, we explore the effect of H2S on the formation of macrophage-derived foam cells. Incubation of monocyte-derived macrophages with oxidized LDL (oxLDL) alone caused significant increases both in intracellular lipids revealed by Oil-red O staining and in intracellular total cholesterol (TC) and esterified cholesterol (EC) concentrations assessed by high-performance liquid chromatography. Sodium hydrosulfide (NaHS, an H2S donor) remarkably abrogated oxLDL-induced intracellular lipid accumulation, and attenuated TC and EC concentrations and EC/TC ratio, whereas DL-propargylglycine (PPG) (a H2S-generating enzyme cystathionine gamma lyase inhibitor) exacerbated lipid accumulation and augmented TC and EC concentrations and EC/TC ratio. Incubation cif 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-oxLDL led to lipoprotein binding and uptake of macrophages, which was blunted by NaHS, but enhanced by PPG. Furthermore, OxLDL markedly induced CD:36, scavenger receptor A (SR-A) and acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) expressions in macrophages, which was suppressed by NaHS (50-200 mu mol/L). Finally, the down-regulations of TC and EC concentrations as well as CD36 and ACAT-1 expressions by NaHS were suppressed by glibenclamide, a K-ATP channel blocker, but facilitated by PD98059, an extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. These results suggested that H2S inhibits foam cell formation by down-regulating CD36, SR-A and ACAT1 expressions via the K-ATP/ERK1/2 pathway in human monocyte-derived macrophages.