Decreased Endogenous Production of Hydrogen Sulfide Accelerates Atherosclerosis
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- Sarathi Mani
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Hongzhu Li
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Ashley Untereiner
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Lingyun Wu
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Guangdong Yang
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Richard C. Austin
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Jeffrey G. Dickhout
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Šárka Lhoták
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Qing H. Meng
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
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- Rui Wang
- From the Department of Biology, Lakehead University, Thunder Bay, ON, Canada (S.M., H.L., R.W.); Department of Health Sciences, Lakehead University, Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada (A.U., L.W.); The School of Kinesiology, Lakehead University, Thunder Bay, ON, Canada (G.Y.); Department of Medicine, Division of Nephrology, McMaster University, St.Joseph’s Healthcare Hamilton and Hamilton Centre for Kidney Research, Hamilton, ON, Canada (R.C.S., J.G.D., S.L.); and...
書誌事項
- 公開日
- 2013-06-25
- DOI
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- 10.1161/circulationaha.113.002208
- 公開者
- Ovid Technologies (Wolters Kluwer Health)
この論文をさがす
説明
<jats:sec> <jats:title>Background—</jats:title> <jats:p> Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H <jats:sub>2</jats:sub> S) in the cardiovascular system. The deficiency of CSE in mice leads to a decreased endogenous H <jats:sub>2</jats:sub> S level, an age-dependent increase in blood pressure, and impaired endothelium-dependent vasorelaxation. To date, there is no direct evidence for a causative role of altered metabolism of endogenous H <jats:sub>2</jats:sub> S in atherosclerosis development. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Six-week-old CSE gene knockout and wild-type mice were fed with either a control chow or atherogenic paigen-type diet for 12 weeks. Plasma lipid profile and homocysteine levels, blood pressure, oxidative stress, atherosclerotic lesion size in the aortic roots, cell proliferation, and adhesion molecule expression were then analyzed. CSE-knockout mice fed with atherogenic diet developed early fatty streak lesions in the aortic root, elevated plasma levels of cholesterol and low-density lipoprotein cholesterol, hyperhomocysteinemia, increased lesional oxidative stress and adhesion molecule expression, and enhanced aortic intimal proliferation. Treatment of CSE-knockout mice with NaHS, but not <jats:italic>N</jats:italic> -acetylcysteine or ezetimibe, inhibited the accelerated atherosclerosis development. Double knockout of CSE and apolipoprotein E gene expression in mice exacerbated atherosclerosis development more than that in the mice with only apolipoprotein E or CSE knockout. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p> Endogenously synthesized H <jats:sub>2</jats:sub> S protects vascular tissues from atherogenic damage by reducing vessel intimal proliferation and inhibiting adhesion molecule expression. Decreased endogenous H <jats:sub>2</jats:sub> S production predisposes the animals to vascular remodeling and early development of atherosclerosis. The CSE/H <jats:sub>2</jats:sub> S pathway is an important therapeutic target for protection against atherosclerosis. </jats:p> </jats:sec>
収録刊行物
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- Circulation
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Circulation 127 (25), 2523-2534, 2013-06-25
Ovid Technologies (Wolters Kluwer Health)