{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T13:55:43Z","timestamp":1792936543727,"version":"4.5.0"},"reference-count":79,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,1,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Circulating cell\u2010free mitochondrial DNA (ccf\u2010mtDNA) is a damage\u2010associated molecular pattern that reflects cell stress responses and tissue damage, but little is known about ccf\u2010mtDNA in preeclampsia. The main objectives of this study were to determine (1) absolute concentrations of ccf\u2010mtDNA in plasma and mitochondrial DNA content in peripheral blood mononuclear cells and (2) forms of ccf\u2010mtDNA transport in blood from women with preeclampsia and healthy controls. In addition, we sought to establish the association between aberrance in circulating DNA\u2010related metrics, including ccf\u2010mtDNA and DNA clearance mechanisms, and the clinical diagnosis of preeclampsia using bootstrapped penalized logistic regression.<\/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                      Absolute concentrations of ccf\u2010mtDNA were reduced in plasma from women with preeclampsia compared with healthy controls (\n                      <jats:italic>P<\/jats:italic>\n                      \u22640.02), while mtDNA copy number in peripheral blood mononuclear cells did not differ between groups (\n                      <jats:italic>P<\/jats:italic>\n                      &gt;0.05). While the pattern of reduced ccf\u2010mtDNA in patients with preeclampsia remained, DNA isolation from plasma using membrane lysis buffer resulted in 1000\u2010fold higher ccf\u2010mtDNA concentrations in the preeclampsia group (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0014) and 430\u2010fold higher ccf\u2010mtDNA concentrations in the control group (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001). Plasma from women with preeclampsia did not induce greater Toll\u2010like receptor\u20109\u2013induced nuclear factor kappa\u2010light\u2010chain enhancer of activated B cells\u2010dependent responses in human embryonic kidney 293 cells overexpressing the human\n                      <jats:italic>TLR\u20109<\/jats:italic>\n                      gene (\n                      <jats:italic>P<\/jats:italic>\n                      &gt;0.05). Penalized regression analysis showed that women with preeclampsia were more likely to have lower concentrations of ccf\u2010mtDNA as well as higher concentrations of nuclear DNA and DNase I compared with their matched controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Women with preeclampsia have aberrant circulating DNA dynamics, including reduced ccf\u2010mtDNA concentrations and DNA clearance mechanisms, compared with gestational age\u2013matched healthy pregnant women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.121.021726","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T09:06:00Z","timestamp":1641891960000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Reduced Maternal Circulating Cell\u2010Free Mitochondrial DNA Is Associated With the Development of Preeclampsia"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2037-8994","authenticated-orcid":false,"given":"Spencer C.","family":"Cushen","sequence":"first","affiliation":[{"name":"Department of Physiology and Anatomy University of North Texas Health Science Center Fort Worth TX"},{"name":"Texas College of Osteopathic Medicine University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2202-1449","authenticated-orcid":false,"given":"Contessa A.","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Physiology and Anatomy University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4011-8401","authenticated-orcid":false,"given":"Jessica L.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Department of Physiology and Anatomy University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-0368","authenticated-orcid":false,"given":"Talisa","family":"Silzer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Blessing","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina M.","family":"Scroggins","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Iowa Carver College of Medicine Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-8017","authenticated-orcid":false,"given":"Mark K.","family":"Santillan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Iowa Carver College of Medicine Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-9714","authenticated-orcid":false,"given":"Donna A.","family":"Santillan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Iowa Carver College of Medicine Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9324-2687","authenticated-orcid":false,"given":"Nicole R.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-8256","authenticated-orcid":false,"given":"Styliani","family":"Goulopoulou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Anatomy University of North Texas Health Science Center Fort Worth TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","unstructured":"American College of O Gynecologists and Task Force on Hypertension in P . 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