{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:05:18Z","timestamp":1788300318909,"version":"build-2803163510"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Preeclampsia, a leading cause of maternal and fetal mortality and morbidity, is characterized by an increase in S\u2010nitrosylated proteins and reactive oxygen species, suggesting a pathophysiologic role for dysregulation in nitrosylation and nitrosative stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Here, we show that mice lacking S\u2010nitrosoglutathione reductase (\n                      <jats:italic>\n                        GSNOR\n                        <jats:sup>\u2212\u2044\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ), a denitrosylase regulating protein S\u2010nitrosylation, exhibit a preeclampsia phenotype, including hypertension, proteinuria, renal pathology, cardiac concentric hypertrophy, decreased placental vascularization, and fetal growth retardation. Reactive oxygen species, NO, and peroxynitrite levels are elevated. Importantly, mass spectrometry reveals elevated placental S\u2010nitrosylated amino acid residues in\n                      <jats:italic>\n                        GSNOR\n                        <jats:sup>\u2212\u2044\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice. Ascorbate reverses the phenotype except for fetal weight, reduces the difference in the S\u2010nitrosoproteome, and identifies a unique set of S\u2010nitrosylated proteins in\n                      <jats:italic>\n                        GSNOR\n                        <jats:sup>\u2212\u2044\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice. Importantly, human preeclamptic placentas exhibit decreased GSNOR activity and increased nitrosative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Therefore, deficiency of GSNOR creates dysregulation of placental S\u2010nitrosylation and preeclampsia in mice, which can be rescued by ascorbate. Coupled with similar findings in human placentas, these findings offer valuable insights and therapeutic implications for preeclampsia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.121.024008","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T05:05:48Z","timestamp":1645506348000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["S\u2010Nitrosoglutathione Reductase Deficiency Causes Aberrant Placental S\u2010Nitrosylation and Preeclampsia"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-7613","authenticated-orcid":false,"given":"Shathiyah","family":"Kulandavelu","sequence":"first","affiliation":[{"name":"Interdisciplinary Stem Cell InstituteUniversity of Miami Miller School of Medicine Miami FL"},{"name":"Department of Pediatrics University of Miami Miller School of Medicine Miami 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