{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:08:27Z","timestamp":1787620107423,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T00:00:00Z","timestamp":1636243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"FWF Austrian Science Fund","doi-asserted-by":"publisher","award":["(DOC 31-B26, W1226 (to RBG), F83 (to RBG)), SFB \u201cLipid hydrolysis\u201d."],"award-info":[{"award-number":["(DOC 31-B26, W1226 (to RBG), F83 (to RBG)), SFB \u201cLipid hydrolysis\u201d."]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that the succinate\u2013SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between the succinate\u2013SUCNR1 axis and placental angiogenesis. In our in vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.<\/jats:p>","DOI":"10.3390\/ijms222112048","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:41:14Z","timestamp":1636317674000},"page":"12048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-4882","authenticated-orcid":false,"given":"Reham","family":"Atallah","sequence":"first","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria"},{"name":"National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6155-5208","authenticated-orcid":false,"given":"Juergen","family":"Gindlhuber","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria"},{"name":"Institute of Chemical Technologies and Analytics, Technische Universit\u00e4t Wien, 1060 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Platzer","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-3700","authenticated-orcid":false,"given":"Thomas","family":"B\u00e4rnthaler","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Tatzl","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Toller","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6138-7566","authenticated-orcid":false,"given":"Jasmin","family":"Strutz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"},{"name":"Institute of Biomedical Science, Carinthia University of Applied Sciences, 9020 Klagenfurt, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8753-4384","authenticated-orcid":false,"given":"Sonja","family":"Rittchen","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Luschnig","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-0312","authenticated-orcid":false,"given":"Ruth","family":"Birner-Gruenberger","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria"},{"name":"Institute of Chemical Technologies and Analytics, Technische Universit\u00e4t Wien, 1060 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-8642","authenticated-orcid":false,"given":"Christian","family":"Wadsack","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-2372","authenticated-orcid":false,"given":"Akos","family":"Heinemann","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1530\/REP-09-0092","article-title":"Regulation of vascular growth and function in the human placenta","volume":"138","author":"Burton","year":"2009","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.placenta.2008.07.004","article-title":"Three-dimensional Arrangement of the Capillary Bed and Its Relationship to Microrheology in the Terminal Villi of Normal Term Placenta","volume":"29","year":"2008","journal-title":"Placenta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.placenta.2003.11.011","article-title":"Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: Differences between placental vasculogenesis and 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