title: Hydrogen sulfide inhibits macrophage-derived foam cell formation.
abstract: Recent evidence indicates that hydrogen sulfide (H(2)S) 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 H(2)S 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 H(2)S donor) remarkably abrogated oxLDL-induced intracellular lipid accumulation, and attenuated TC and EC concentrations and EC/TC ratio, whereas dl-propargylglycine (PPG) (a H(2)S-generating enzyme cystathionine gamma lyase inhibitor) exacerbated lipid accumulation and augmented TC and EC concentrations and EC/TC ratio. Incubation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-oxLDL led to lipoprotein binding and uptake of macrophages, which was blunted by NaHS, but enhanced by PPG. Furthermore, OxLDL markedly induced CD36, scavenger receptor A (SR-A) and acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) expressions in macrophages, which was suppressed by NaHS (50-200 μmol/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 H(2)S 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.
authors.affiliation: Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang City, Hunan 421001, P. R. China.
authors.forename: Zhan-Zhi
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Li
authors.forename: Ren
authors.initials: R
authors.lastname: Wang
authors.forename: Jian-Miao
authors.initials: JM
authors.lastname: Tan
authors.forename: Xuan
authors.initials: X
authors.lastname: Cao
authors.forename: Rong
authors.initials: R
authors.lastname: Suo
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Jiang
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000096:biosynthesis; D000480:Alkynes / Q000378:metabolism; D018955:CD36 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects*; D015870:Gene Expression; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis; D013440:Sulfides / Q000378:metabolism
chemical_list: D000480:Alkynes; D018955:CD36 Antigens; D004791:Enzyme Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; D013440:Sulfides; C099252:oxidized low density lipoprotein; C009055:propargylglycine; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005998:Glycine; D006862:Hydrogen Sulfide