Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia.
Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia.
复制标题
DOI：
10.1042/cs20120130
复制
发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Webb RC
中科院分区：
文献类型：
--
作者：
Goulopoulou S;Matsumoto T;Bomfim GF;Webb RC
Emerging evidence suggests that in addition of being the “power houses” of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mitochondrial DNA (mtDNA) that acts via Toll-like receptor 9 (TLR9), 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 in a similar fashion with bacterial DNA stems from evolutionary conserved similarities between bacteria and mitochondria. Mitochondrial DNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. Preeclampsia (PE) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The etiology 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 stimulate TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and intrauterine 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.
