{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:23:23Z","timestamp":1793996603891,"version":"4.8.0"},"reference-count":59,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>High gestational weight gain (GWG) is a cardiovascular risk factor and may disturb neonatal endothelial function. Long non\u2010coding RNAs (lncRNAs) regulate gene expression epigenetically and can modulate endothelial function. Endothelial colony forming cells (ECFCs), circulating endothelial precursors, are a recruitable source of endothelial cells and sustain endothelial function, vascular growth and repair. We here investigated whether higher GWG affects neonatal ECFC function and elucidated the role of lncRNAs herein. Wound healing of umbilical cord blood\u2010derived ECFCs after pregnancies with GWG &lt;13 kg <jats:italic>versus<\/jats:italic> &gt;13\u00a0kg was determined in a scratch assay and based on monolayer impedance after electric wounding (electric cell\u2010substrate impedance sensing, ECIS). LncRNA expression was analysed by RNA sequencing. The function of killer cell lectin\u2010like receptor K1 antisense RNA (<jats:italic>KLRK1\u2010AS1<\/jats:italic>) was investigated after siRNA\u2010based knockdown. Closure of the scratch was delayed by 25% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.041) in the higher GWG group and correlated inversely with GWG (<jats:italic>R<\/jats:italic>\u00a0=\u00a0\u22120.538, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012) in all subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a022). Similarly, recovery of the monolayer barrier after electric wounding was delayed (\u221211% after 20\u00a0h; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014; <jats:italic>n<\/jats:italic>\u00a0=\u00a015). Several lncRNAs correlated with maternal GWG, the most significant one being <jats:italic>KLRK1\u2010AS1<\/jats:italic> (log<jats:sub>2<\/jats:sub> fold change\u00a0=\u00a0\u22120.135, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, <jats:italic>n<\/jats:italic>\u00a0=\u00a035). <jats:italic>KLRK1\u2010AS1<\/jats:italic> knockdown (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) reduced barrier recovery after electric wounding by 21% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.029) and <jats:italic>KLRK1\u2010AS1<\/jats:italic> expression correlated with the time required for wound healing for both scratch (<jats:italic>R<\/jats:italic>\u00a0=\u00a00.447, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.033) and impedance\u2010based assay (<jats:italic>R<\/jats:italic>\u00a0=\u00a00.629, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014). Higher GWG reduces wound healing of neonatal ECFCs, and lower levels of the lncRNA <jats:italic>KLRK1\u2010AS1<\/jats:italic>\u00a0may underlie this.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15649-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Maternal cardiovascular risk factors such as diabetes, obesity and smoking in pregnancy disturb fetal endothelial function, and we here investigated whether also high gestational weight gain (GWG) has an impact on fetal endothelial cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Circulating endothelial progenitor cells (endothelial colony forming cells, ECFCs) are highly abundant in the neonatal blood stream and serve as a circulating pool for vascular growth and repair.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We revealed that higher GWG delays wound healing capacity of ECFCs <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We identified the regulatory RNA lncRNA <jats:italic>KLRK1\u2010AS1<\/jats:italic> as a link between GWG and delayed ECFC wound healing.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data show that high GWG, independent of pre\u2010pregnancy BMI, affects neonatal ECFC function.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284871","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T11:07:45Z","timestamp":1689851265000},"page":"3961-3974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Higher gestational weight gain delays wound healing and reduces expression of long non\u2010coding RNA <i>KLRK1\u2010AS1<\/i> in neonatal endothelial progenitor cells"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-8280","authenticated-orcid":false,"given":"Elisa","family":"Weiss","sequence":"first","affiliation":[{"name":"Perinatal Research Laboratory, Department of Obstetrics and Gynaecology Medical University of Graz Graz Austria"},{"name":"Research Unit Early Life Determinants (ELiD) Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-9543","authenticated-orcid":false,"given":"Anna","family":"Schr\u00fcfer","sequence":"additional","affiliation":[{"name":"Perinatal Research Laboratory, Department of Obstetrics and Gynaecology Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-0454","authenticated-orcid":false,"given":"Carolina","family":"Tocantins","sequence":"additional","affiliation":[{"name":"Perinatal Research Laboratory, Department of Obstetrics and Gynaecology Medical University of Graz Graz Austria"},{"name":"CNC\u2010Center for Neuroscience and Cell Biology, CIBB\u2010Centre for Innovative Biomedicine and Biotechnology University of Coimbra Coimbra Portugal"},{"name":"PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC) University of Coimbra Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2161-9676","authenticated-orcid":false,"given":"Mariana Simoes","family":"Diniz","sequence":"additional","affiliation":[{"name":"Perinatal Research Laboratory, Department of Obstetrics and Gynaecology Medical University of Graz Graz 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Physiology Amsterdam University Medical Centers, Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Microcirculation Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1228-2946","authenticated-orcid":false,"given":"Azra","family":"Kulovic\u2010Sissawo","sequence":"additional","affiliation":[{"name":"Perinatal Research Laboratory, Department of Obstetrics and Gynaecology Medical University of Graz Graz Austria"},{"name":"Research Unit Early Life Determinants (ELiD) Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-4181","authenticated-orcid":false,"given":"Richard","family":"Saffery","sequence":"additional","affiliation":[{"name":"Molecular Immunity, Infection and Immunity Theme Murdoch Children's Research Institute Parkville Victoria Australia"},{"name":"Department of 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