ABSTRACT
Inadequate trophoblastic invasion is considered as one of hallmarks of preeclampsia (PE), which is characterized by newly onset of hypertension (>140/90 mmHg) and proteinuria (>300 mg in a 24-h urine) after 20 weeks of gestation. Accumulating evidence has indicated that long noncoding RNAs are aberrantly expressed in PE, whereas detailed mechanisms are unknown. In the present study, we showed that lncRNA Taurine upregulated 1 (TUG1) were downregulated in preeclamptic placenta and in HTR8/SVneo cells under hypoxic conditions, together with reduced enhancer of zeste homolog2 (EZH2) and embryonic ectoderm development (EED) expression, major components of polycomb repressive complex 2 (PRC2), as well as activation of Nodal/ALK7 signalling pathway. Mechanistically, we found that TUG1 bound to PRC2 (EZH2/EED) in HTR8/SVneo cells and weakened TUG1/PRC2 interplay was correlated with upregulation of Nodal expression via decreasing H3K27me3 mark at the promoter region of Nodal gene under hypoxic conditions. And activation of Nodal signalling prohibited trophoblast invasion via reducing MMP2 levels. Overexpression of TUG1 or EZH2 significantly attenuated hypoxia-induced reduction of trophoblastic invasiveness via negative modulating Nodal/ALK7 signalling and rescuing expression of its downstream target MMP2. These investigations might provide some evidence for novel mechanisms responsible for inadequate trophoblastic invasion and might shed some light on identifying future therapeutic targets for PE.
Subject(s)
Pre-Eclampsia , RNA, Long Noncoding , Activin Receptors, Type I/metabolism , Cell Movement/genetics , Cell Proliferation/genetics , Female , Humans , Hypoxia/genetics , Hypoxia/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Nodal Protein/metabolism , Polycomb Repressive Complex 2/metabolism , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Pregnancy , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Taurine/metabolism , Transforming Growth Factor beta/metabolism , Trophoblasts/metabolismABSTRACT
The purpose of this study was to assess the value of echocardiography for intraoperative guidance during closure of perimembranous ventricular septal defects (pmVSD) and to assess outcomes of these patients. We identified and assessed 78 patients who underwent 2- and 3-dimensional echocardiography-guided mini-invasive per-atrial closure of pmVSD in the cardiac surgery department of our institution, from February 2016 to August 2018, and 76 patients who underwent transcatheter closure of VSD guided by fluoroscopy at the pediatric department (percutaneous control group). All the patients underwent echocardiography. Their clinical data were retrospectively reviewed and analyzed. All patients were followed up using transthoracic echocardiography (TTE) for a maximum of 24 months after the closure. All patients underwent successful device implantation. Echocardiography showed that the major immediate complications included residual shunt, pericardial effusion, and tricuspid regurgitation in the per-atrial group. During the mid-term follow-up period, TTE revealed that the most common complication was tricuspid regurgitation (non-preexisting). There were no cases of VSD recurrence, device displacement, valvular injury, malignant arrhythmias, hemolysis, or death. Moreover, according to the TTE data, the intracardiac structure of the patients were improved. Compared to the control group, the intracardiac manipulation time was shorter and the number of patients with residual shunts, redeployment of devices, or immediate new tricuspid regurgitations was fewer when using 2- and 3-dimensional echocardiography. However, the procedure time in the per-atrial group was slightly longer than that in the control group. Two- and 3-dimensional echocardiography are feasible monitoring tools during mini-invasive per-atrial VSD closure. The short- and mid-term follow-up showed satisfactory results compared to fluoroscopy.
