Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Science-University of Barcelona, Internal Medicine Service-Hospital Clínic of Barcelona, Barcelona, Spain.
CIBERER, U722, Madrid, Spain.
J Antimicrob Chemother. 2017 Sep 1;72(9):2578-2586. doi: 10.1093/jac/dkx187.
HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis.
To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications.
This controlled, single-site, observational study without intervention included 26 HIV-infected pregnant women on HAART and 18 control pregnancies and their newborns. Maternal PBMCs and neonatal cord blood mononuclear cells (CBMCs) were isolated at the first trimester of gestation and at delivery. The placenta was homogenized at 5% w/v. Mitochondrial dynamics, fusion events [mitofusin 2 (Mfn2)/β-actin] and fission events [dynamin-related protein 1 (Drp1/β-actin)] and apoptosis (caspase 3/β-actin) were assessed by western blot analysis.
Obstetric complications were significantly more frequent in pregnancies among HIV-infected women [OR 5.00 (95% CI 1.21-20.70)]. Mfn2/β-actin levels in PBMCs from controls significantly decreased during pregnancy (202.13 ± 57.45%), whereas cases maintained reduced levels from the first trimester of pregnancy and no differences were observed in CBMCs. Mfn2/β-actin and Drp1/β-actin contents significantly decreased in the placenta of cases. Caspase 3/β-actin levels significantly increased during pregnancy in PBMCs of cases (50.00 ± 7.89%), remaining significantly higher than in controls. No significant differences in caspase 3/β-actin content of neonatal CBMCs were observed, but there was a slight increased trend in placenta from cases.
HIV- and HAART-mediated mitochondrial damage may be enhanced by decreased mitochondrial dynamics and increased apoptosis in maternal and placental compartments but not in the uninfected fetus. However, direct effects on mitochondrial dynamics and implication of apoptosis were not demonstrated in adverse obstetric outcomes.
HIV 感染和高效抗逆转录病毒治疗（HAART）会引发遗传和功能上的线粒体改变，导致细胞死亡和不良的临床症状。线粒体动力学使线粒体更新和受损线粒体的降解成为可能，这可能导致细胞凋亡。
评估 HIV 感染的 HAART 孕妇的线粒体动力学和细胞凋亡标志物，并确定它们与产科并发症的潜在关联。
这是一项无干预的对照、单站点、观察性研究，共纳入 26 名 HIV 感染的 HAART 孕妇、18 名对照孕妇及其新生儿。在妊娠早期和分娩时分离孕妇的外周血单核细胞（PBMC）和新生儿脐血单核细胞（CBMC）。胎盘以 5%w/v 匀浆。通过 Western blot 分析评估线粒体动力学、融合事件（线粒体融合蛋白 2 [Mfn2]/β-肌动蛋白）和分裂事件（动力相关蛋白 1 [Drp1]/β-肌动蛋白）以及细胞凋亡（半胱天冬酶 3/β-肌动蛋白）。
HIV 感染孕妇的产科并发症发生率明显更高[比值比 5.00（95%置信区间 1.21-20.70）]。对照组 PBMC 中的 Mfn2/β-肌动蛋白水平在妊娠期间显著下降（202.13±57.45%），而病例组则从妊娠早期开始维持低水平，CBMC 中未见差异。病例组胎盘的 Mfn2/β-肌动蛋白和 Drp1/β-肌动蛋白含量显著下降。病例组 PBMC 中的半胱天冬酶 3/β-肌动蛋白水平在妊娠期间显著升高（50.00±7.89%），仍明显高于对照组。新生儿 CBMC 中 caspase 3/β-肌动蛋白含量无显著差异，但胎盘中存在轻微升高趋势。
HIV 和 HAART 介导的线粒体损伤可能通过母体和胎盘部位线粒体动力学降低和细胞凋亡增加而加重，但未感染胎儿的线粒体动力学和细胞凋亡未见明显变化。然而，线粒体动力学和细胞凋亡在不良产科结局中的直接影响并未得到证实。
