{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:34:40Z","timestamp":1791974080382,"version":"4.4.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,6,25]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              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\n              <jats:sub>2<\/jats:sub>\n              S), a gaseous messenger produced mainly by cystathionine \u03b3-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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Plasma levels of H\n              <jats:sub>2<\/jats:sub>\n              S were significantly decreased in women with preeclampsia (\n              <jats:italic>P<\/jats:italic>\n              &lt;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\n              <jats:sc>DL<\/jats:sc>\n              -propargylglycine reduced placental growth factorproduction from first-trimester (8\u201312 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\n              <jats:sc>DL<\/jats:sc>\n              -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\n              <jats:sub>2<\/jats:sub>\n              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\n              <jats:sc>DL<\/jats:sc>\n              -propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H\n              <jats:sub>2<\/jats:sub>\n              S production.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              These results imply that endogenous H\n              <jats:sub>2<\/jats:sub>\n              S is required for healthy placental vasculature and that a decrease in CSE\/H\n              <jats:sub>2<\/jats:sub>\n              S activity may contribute to the pathogenesis of preeclampsia. (Circulation. 2013;127:2514-2522.)\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.113.001631","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T05:06:45Z","timestamp":1369372005000},"page":"2514-2522","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":243,"title":["Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine \u03b3-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia"],"prefix":"10.1161","volume":"127","author":[{"given":"Keqing","family":"Wang","sequence":"first","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakil","family":"Ahmad","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Cai","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Rennie","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Crispi","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Baily","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Miller","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Cudmore","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W. F.","family":"Hadoke","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Gratac\u00f3s","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Buhimschi","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin S.","family":"Buhimschi","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Ahmed","sequence":"additional","affiliation":[{"name":"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,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.21.6008"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908047106"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6270fje"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31802e27a0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705891104"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3781"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.11.081"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.04.162"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1162667"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.11.003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.3912"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/14034940500217037"},{"key":"e_1_3_3_14_2","first-page":"177","article-title":"The role of the spiral arteries in the pathogenesis of preeclampsia.","volume":"1","author":"Brosens IA","year":"1972","unstructured":"Brosens IA, Robertson WB, Dixon HG. The role of the spiral arteries in the pathogenesis of preeclampsia. Obstet Gynecol Annu. 1972;1:177\u2013191.","journal-title":"Obstet Gynecol Annu"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2006.00882.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0371237"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2010.10.004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031884"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055352"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(98)70021-3"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.111"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.1.77"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.12.052"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.6126"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.7621"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.895458"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-7-10"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023788"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000147365.86159.f5"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs137"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470942390.mo100149"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000243989.46006.b9"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.660134"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.1406"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.2527\/1995.7361839x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17189"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.109.147595"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0548"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0773"},{"key":"e_1_3_3_40_2","first-page":"180","article-title":"Development of structures and transport functions in the mouse placenta.","volume":"20","author":"Watson ED","year":"2005","unstructured":"Watson ED, Cross JC. Development of structures and transport functions in the mouse placenta. Physiology (Bethesda). 2005;20:180\u2013193.","journal-title":"Physiology (Bethesda)"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9306"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.008953"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.02.014"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.01.001"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20110672"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-012-9261-5"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031244"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1028-4559(09)60028-0"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb03212.x"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.113.001631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:43:44Z","timestamp":1715582624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.113.001631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,25]]},"references-count":48,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2013,6,25]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.113.001631"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.113.001631","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,25]]},"assertion":[{"value":"2012-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}