{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:04:39Z","timestamp":1789448679393,"version":"build-2803163510"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"7","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:p>Emerging evidence suggests that in addition to being the \u2018power houses\u2019 of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mtDNA (mitochondrial DNA) that acts via TLR9 (Toll-like receptor 9), a pattern recognition receptor of the immune system which detects bacterial and viral DNA but not vertebrate DNA. The ability of mtDNA to activate TLR9\u00a0in a similar fashion to bacterial DNA stems from evolutionarily conserved similarities between bacteria and mitochondria. mtDNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. PE (pre-eclampsia) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The aetiology of PE is unknown and removal of the placenta is the only effective cure. Placentas from women with PE show exaggerated necrosis of trophoblast cells, and circulating levels of mtDNA are higher in pregnancies with PE. Accordingly, we propose the hypothesis that exaggerated necrosis of trophoblast cells results in the release of mtDNA, which stimulates TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and IUGR (intra-uterine growth restriction). The proposed hypothesis implicates mtDNA in the development of PE via activation of the immune system and may have important preventative and therapeutic implications, because circulating mtDNA may be potential markers of early detection of PE, and anti-TLR9 treatments may be promising in the management of the disease.<\/jats:p>","DOI":"10.1042\/cs20120130","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T09:12:12Z","timestamp":1339060332000},"page":"429-435","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia"],"prefix":"10.1042","volume":"123","author":[{"given":"Styliani","family":"Goulopoulou","sequence":"first","affiliation":[{"name":"Department of Physiology, Georgia Health Sciences University, Augusta, GA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele\u00a0F.","family":"Bomfim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.\u00a0Clinton","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Physiology, Georgia Health Sciences University, Augusta, GA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,6,7]]},"reference":[{"key":"2021113010251881400_B1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1067\/mob.2000.107928","article-title":"Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy","volume":"183","author":"National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy","year":"2000","journal-title":"Am. 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