title: The interaction of estrogen and CSE/H2S pathway in the development of atherosclerosis.
abstract: Both estrogen and hydrogen sulfide (H2S) have been shown to inhibit the development of atherosclerosis. We previously reported that cystathionine γ-lyase knockout (CSE-KO) male mice develop atherosclerosis earlier than male wild-type (WT) mice. The present study investigated the interaction of CSE/H2S pathway and estrogen on the development of atherosclerosis in female mice. Plasma estrogen levels were significantly lower in female CSE-KO mice than in female WT mice. NaHS treatment had no effect on plasma estrogen levels in both WT and CSE-KO female mice. After CSE-KO and WT female mice were fed with atherogenic diet for 12 wk, plasma lipid levels were significantly increased and triglyceride levels decreased compared with those of control diet-fed mice. Atherogenic diet induced more atherosclerotic lesion, oxidative stress, intracellular adhesion molecule-1 (ICAM-1), and NF-κB in CSE-KO mice than in WT mice. Estrogen treatment of atherogenic diet-fed WT mice attenuated hypercholesterolemia, oxidative stress, ICAM-1 expression, and NF-κB in WT mice but not in atherogenic diet-fed CSE-KO mice. Furthermore, H2S production in both the liver and vascular tissues was enhanced by estrogen in WT mice but not in CSE-KO mice. It is concluded that the antiatherosclerotic effect of estrogen is mediated by CSE-generated H2S. This study provides new insights into the interaction of H2S and estrogen signaling pathways on the regulation of cardiovascular functions.NEW & NOTEWORTHYFemale cystathionine γ-lyase (CSE)-knockout mice have significantly lower plasma estrogen levels and more severe early atherosclerotic lesion than female wild-type mice. H2S production in liver and vascular tissues is enhanced by estrogen via its stimulatory effect on CSE activity. The antiatherosclerotic effect of estrogen is mediated by CSE-generated H2S.
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.|Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Sarathi
authors.initials: S
authors.lastname: Mani
authors.affiliation: Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.|Health Sciences North Research Institute, Sudbury, Ontario, Canada; and.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Fu
authors.affiliation: Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.|Department of Biology, Laurentian University, Sudbury, Ontario, Canada.
authors.forename: Tian
authors.initials: T
authors.lastname: Shuang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada; rui.wang@laurentian.ca.|Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.|Department of Biology, Laurentian University, Sudbury, Ontario, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D003542:Cystathionine gamma-Lyase; D004036:Diet, Atherogenic; D004967:Estrogens / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D006862:Hydrogen Sulfide; D020672:I-kappa B Proteins / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D004967:Estrogens; D020672:I-kappa B Proteins; D008055:Lipids; D051996:Transcription Factor RelA; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: atherosclerosis; estrogen; hydrogen sulfide; oxidative stress; smooth muscle cells