{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:20:59Z","timestamp":1792977659506,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG VE 490\/15\u20101"],"award-info":[{"award-number":["DFG VE 490\/15\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Preeclampsia, a pregnancy\u2010related hypertensive disorder, is associated with endothelial dysfunction and increased cardiovascular risk of the offspring in adulthood. In preeclampsia, endothelial colony\u2010forming cells (ECFC) are reduced in number and function. Recently, we have shown that miR\u20101270, which is involved in cancer in vitro proliferation, migration, and tumor progression, is downregulated in fetal ECFC from preeclamptic pregnancies. We now hypothesize that miR\u20101270 dysregulation contributes to vascular endothelial dysfunction occurring after preeclampsia via ATM (ataxia telangiectasia mutated) overexpression, the key kinase of DNA damage repair. Here, we show that miR\u20101270\u00a0silencing in normal ECFC and downregulation in preeclamptic ECFC are accompanied by an increase in the expression levels of\n                    <jats:italic>ATM<\/jats:italic>\n                    . Furthermore, ATM activation correlates with upregulated tyrosine kinase Src leading to phosphorylation and internalization of VE\u2010cadherin (vascular endothelial\u2010cadherin) which subsequently compromises endothelial barrier permeability and morphodynamic cell parameters. Treatment with specific ATM inhibitors reveals a novel role of ATM upstream of tyrosine kinase Src activation. Subsequently, Src phosphorylation and internalization of VE\u2010cadherin compromise endothelial barrier permeability. Our findings suggest that downregulation of miR\u20101270 contributes to impaired ECFC function via the associated ATM overexpression, which further identifies ATM as a novel and critical factor for ECFC defects in preeclampsia. Our study provides new insights into the understanding of ECFC impairment associated with cardiovascular risk in preeclamptic offspring and identifies potential novel therapeutic targets.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200040rr","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T12:20:47Z","timestamp":1654086047000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Downregulation of miR\u20101270 mediates endothelial progenitor cell function in preeclampsia: Role for ATM in the Src\/VE\u2010cadherin axis"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-2373","authenticated-orcid":false,"given":"Bianca","family":"Schr\u00f6der\u2010Heurich","sequence":"first","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"B\u00fcder","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Meyer","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu Huong","family":"Vu","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"},{"name":"Department of Obstetrics and Gynecology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Richter","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanya","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Brodowski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin S.","family":"von Kaisenberg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-5695","authenticated-orcid":false,"given":"Frauke","family":"von Versen\u2010H\u00f6ynck","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit Hannover Medical School  Hannover Germany"},{"name":"Department of Obstetrics and Gynecology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313276"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/953150"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1016248"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0146-0005(00)80050-6"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.941203"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-3093"},{"issue":"4","key":"e_1_2_14_8_1","first-page":"309","article-title":"Endothelial dysfunction. 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