Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

<div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10^-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10^-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div

Pre-eclampsia: evidence of altered ventricular repolarization by standard ECG parameters and QT dispersion.

Pre-eclampsia complicates approximately 6-8\% of all pregnancies. Epidemiologic studies have demonstrated a relationship between pre-eclampsia and cardiac morbidity and mortality later in life, but the effect of pre-eclampsia on electrical cardiac activity during the acute phase has not yet been understood. The aim of this study was to investigate ECG alterations during pre-eclampsia. Prepartum ECGs of 76 consecutive pre-eclamptic women were compared with those of 76 healthy pregnant women. All of the routine ECG parameters were considered, and ventricular repolarization was assessed by QT interval and QT dispersion (QTd). Pregnancies complicated by pre-eclampsia showed a significant alteration of ventricular repolarization compared with the control group. Among ECG parameters, QT and QTc intervals and QTd were more prolonged in pre-eclamptic women. Multivariate analysis also showed that pre-eclampsia was the only independent determinant of QTd. In conclusion, pre-eclampsia has a significant effect on ventricular repolarization. This alteration could, in part, explain the increased cardiovascular risk of women with a history of pre-eclampsia. Further studies are necessary to confirm the relationship between ventricular repolarization abnormalities and increased cardiovascular risk later in life

Emotional Awareness in Depressive and Anxiety Symptoms in Youth: A Meta-Analytic Review

Emotion regulation is assumed to play an important role in depressive and anxiety symptoms in youth. However, the role of core components of emotion regulation, such as emotional awareness, is not well understood so far. Thus this meta-analysis aimed to examine the relationship between depressive and anxiety symptoms with emotional awareness in youth. A systematic literature search (PsycINFO, Medline, Google Scholar) identified 21 studies, from which 34 effect sizes were extracted. Results from random effects models showed that difficulties in emotional awareness were significantly correlated with a medium effect size for each, depressive and anxiety symptoms separately, and for their combined effects (overall outcome). Additionally, further analyses revealed that age was a significant moderator of the relationship between emotional awareness with depressive and anxiety symptoms, with younger samples (mean age ≤ 12 years) showing a stronger association between difficulties in emotional awareness and depressive and anxiety symptoms as compared to older samples (mean age > 12 years). The results suggest that emotional awareness may be of relevance for depressive and anxiety symptoms in youth. Future work is required to examine longitudinal developments, moderators, and mediators in multi-method approaches. Moreover, children and adolescents may benefit from interventions that aim to enhance emotional awareness

Invisible side of emotions: somato-motor responses to affective facial displays in alexithymia

According to recent theories, the detection of emotions involves somatic experiences. In this study, we investigated the relation between somatic responses to affective stimuli, emotion perception, and alexithymia. Variations in automatic rapid facial reactions (RFRs) were measured in a selected population of participants with high and low levels of alexithymia (HA and LA, respectively). Electromyographic activity was recorded from the corrugator supercilii and the zygomaticus major, while participants performed a gender classification task on faces expressing various emotional states. LA participants showed congruent RFRs in response to both fearful and happy stimuli. On the other hand, HA participants did not show congruent RFRs in response to fearful faces. They showed congruent, but delayed, RFRs in response to happy faces. These results provide evidence of a deficit in somato-motor emotional processing in people with high alexithymic personality traits, and thus support the hypothesis that alexithymia is associated with a deficit in emotional embodiment