Hydrogen sulfide inhibits macrophage-derived foam cell formation

Exp Biol Med (Maywood). 2011 Feb;236(2):169-76. doi: 10.1258/ebm.2010.010308.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA C-Acetyltransferase / biosynthesis
  • Alkynes / metabolism
  • CD36 Antigens / biosynthesis
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cystathionine gamma-Lyase / antagonists & inhibitors
  • Cytoplasm / chemistry
  • Down-Regulation
  • Enzyme Inhibitors / metabolism
  • Foam Cells / drug effects*
  • Gene Expression
  • Glycine / analogs & derivatives
  • Glycine / metabolism
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Lipids / analysis
  • Lipoproteins, LDL / metabolism
  • Macrophages / drug effects*
  • Scavenger Receptors, Class A / biosynthesis
  • Sulfides / metabolism


  • Alkynes
  • CD36 Antigens
  • Enzyme Inhibitors
  • Lipids
  • Lipoproteins, LDL
  • Scavenger Receptors, Class A
  • Sulfides
  • oxidized low density lipoprotein
  • propargylglycine
  • ACAT1 protein, human
  • Acetyl-CoA C-Acetyltransferase
  • Cystathionine gamma-Lyase
  • sodium bisulfide
  • Glycine
  • Hydrogen Sulfide