Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice.
OBJECTIVE
We explored the effect of hydrogen sulfide (H(2)S) on atherosclerotic progression, particularly on intracellular adhesion molecule-1 (ICAM-1) in apolipoprotein-E knockout (apoE(-/-)) mice and human umbilical vein endothelial cells (HUVECs).


RESULTS
ApoE(-/-) mice were treated with sodium hydrosulfide (NaHS) or DL-propargylglycine (PPG); HUVECs were pretreated with NaHS. Compared with control mice, apoE(-/-) mice showed decreased plasma H(2)S level and aortic H(2)S production but increased plasma ICAM-1 and aortic ICAM-1 protein and mRNA. Compared with apoE(-/-) mice, apoE(-/-)+NaHS mice showed increased plasma H(2)S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE(-/-)+PPG mice showed decreased plasma H(2)S level but enlarged plaque size and increased plasma and aortic ICAM-1 levels. NaHS suppressed ICAM-1 expression in tumor necrosis factor (TNF)-alpha-treated HUVECs. NaHS inhibited IkappaB degradation and NF-kappaB nuclear translocation in HUVECs treated with TNF-alpha.


CONCLUSIONS
The vascular CSE/H(2)S pathway was disturbed in apoE(-/-) mice. H(2)S exerted an antiatherogenic effect and inhibited ICAM-1 expression in apoE(-/-) mice. H(2)S inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kappaB pathway.
Wang
Yanfei
Y
Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West district, Beijing 100034, PR China.
Zhao
Xia
X
Jin
Hongfang
H
Wei
Hongling
H
Li
Wei
W
Bu
Dingfang
D
Tang
Xiuying
X
Ren
Yali
Y
Tang
Chaoshu
C
Du
Junbao
J
D021581:Active Transport, Cell Nucleus; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000480:Alkynes; D001057:Apolipoproteins E; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D008055:Lipids; D016328:NF-kappa B; D012333:RNA, Messenger; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C009055:propargylglycine; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005998:Glycine; D006862:Hydrogen Sulfide