Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia
-
- Keqing Wang
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Shakil Ahmad
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Meng Cai
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Jillian Rennie
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Takeshi Fujisawa
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Fatima Crispi
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- James Baily
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Mark R. Miller
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Melissa Cudmore
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Patrick W. F. Hadoke
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Rui Wang
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Eduard Gratacós
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Irina A. Buhimschi
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Catalin S. Buhimschi
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
-
- Asif Ahmed
- From the Vascular Medicine Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom (K.W., S.A., M.C., A.A.); Gustav Born Centre for Vascular Biology, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (K.W., S.A., M.C., J.R., T.K., J.B., M.R.M., M.C., P.W.F.H., A.A.); Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Spain (F.C., E.G.); Lakehead University, Thunder Bay,...
書誌事項
- 公開日
- 2013-06-25
- DOI
-
- 10.1161/circulationaha.113.001631
- 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> The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H <jats:sub>2</jats:sub> S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Plasma levels of H <jats:sub>2</jats:sub> S were significantly decreased in women with preeclampsia ( <jats:italic>P</jats:italic> <0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by <jats:sc>DL</jats:sc> -propargylglycine reduced placental growth factorproduction from first-trimester (8–12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of <jats:sc>DL</jats:sc> -propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H <jats:sub>2</jats:sub> S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by <jats:sc>DL</jats:sc> -propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H <jats:sub>2</jats:sub> S production. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p> These results imply that endogenous H <jats:sub>2</jats:sub> S is required for healthy placental vasculature and that a decrease in CSE/H <jats:sub>2</jats:sub> S activity may contribute to the pathogenesis of preeclampsia. (Circulation. 2013;127:2514-2522.) </jats:p> </jats:sec>
収録刊行物
-
- Circulation
-
Circulation 127 (25), 2514-2522, 2013-06-25
Ovid Technologies (Wolters Kluwer Health)