miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia.

MicroRNAs (miRNAs) are non-coding small RNA molecules that can be secreted into the circulation and which exist in remarkably stable forms. Circulating miRNAs regulate numerous biological process and are aberrantly expressed in pathological conditions. Differentially expressed circulating miRNAs have received attention as potential biomarkers for many diseases. In this study, we revealed that miR-515-5p was significantly upregulated in maternal serum from preeclampsia patients in comparison to normal pregnant women. Bioinformatics prediction and a dual-luciferase reporter gene assay revealed that miR-515-5p directly targets the X-linked inhibitor of apoptosis protein (XIAP) 3'-untranslated region. In addition, the overexpression of miR-515-5p inhibited the proliferation and invasion of HTR-8/SVneo trophoblast cells. The decreased XIAP expression and reduced epithelial-mesenchymal transition (EMT) were observed in the preeclamptic placenta. Collectively, miR-515-5p may play critical roles in the pathogenesis of preeclampsia through suppression of XIAP, and serum miR-515-5p may act as a potential biomarker for preeclampsia.

Possible prevention of post-partum depression by intake of omega-3 polyunsaturated fatty acids and its relationship with interleukin 6.

AIM: This study examined whether the intake of omega-3 polyunsaturated fatty acids (PUFA) prevented post-partum depression and if interleukin 6 (IL-6) was involved in this effect. We hypothesized that omega-3 supplementation has a protective effect against post-partum depression. METHODS: We measured eicosapentaenoic acid (EPA), the arachidonic acid (AA)/EPA ratio, and IL-6 in 80 singleton pregnant women during the first and second trimesters, and post-partum. The women also completed a dietary questionnaire, and post-partum depression was measured using the Edinburgh Postnatal Depression Scale (EPDS). We examined the correlations between the frequency of eating fish and EPA, the AA/EPA ratio and IL-6 in the first and second trimesters, and post-partum. We also investigated the correlation between the EPDS and the EPA, the AA/EPA ratio and IL-6. RESULTS: The frequency of eating fish was significantly correlated with EPA in the second trimester and post-partum and with the AA/EPA ratio in the second trimester. There was no correlation between IL-6 levels and the frequency of eating fish. Post-partum levels of EPA and the AA/EPA ratio were higher in the EPDS >7 group than in the EPDS ≤7 group. In the second trimester, a higher AA/EPA ratio was associated with EPDS >7. IL-6 levels did not differ between the two groups. CONCLUSION: In conclusion, a low dietary intake of omega-3 PUFA during pregnancy was correlated with lower EPA levels, which tended to lead to post-partum depression. The relationship between the IL-6 level and the pathogenesis of post-partum depression was unclear from the results of this study.

Appropriate delivery method for cardiac disease pregnancy based on noninvasive cardiac monitoring.

Background There are numerous significant physiological changes occurring in circulation during labor. To detect these rapid hemodynamic changes, invasive and intermittent measurement techniques are not reliable. To suggest a suitable delivery method for pregnancy with cardiac disease, this study analyzed how each delivery method influences cardiac function using a noninvasive and continuous measurement technique. Methods A prospective study was accomplished at the National Cerebral and Cardiovascular Center in Japan from October 1, 2014, to November 30, 2018. The classification of the healthy heart pregnant women was according to the delivery method: vaginal delivery (VD) without epidural anesthesia, VD with epidural anesthesia, and caesarean section (CS). The hemodynamic parameters cardiac index (CI), stroke volume index (SI), and heart rate (HR) were evaluated regularly throughout delivery by noninvasive electrical cardiometry monitor. Results Ten cases were examined for each group. CI and HR were significantly increased before VD, while the increase in CI and HR was mild in the epidural group in comparison to the nonepidural group. SI was increased toward the delivery in the epidural group, and it was constant in the nonepidural group. However, there was no alteration in the level of outcomes of the two groups. In CS, SI increased and HR decreased before delivery. After delivery, SI continued to increase, while HR did not change but CI increased. Conclusion In VD, the increase in venous circulation according to the autotransfusion is managed by increasing HR. By epidural anesthesia, the increase in HR was suppressed and SI was increased. However, as epidural anesthesia increases the vascular capacity, the level of SI outcome was comparable. In CS, the HR was decreased because of the spinal anesthesia and the SI was increased because of many factors like hydration. As there are many factors to control in CS, VD with epidural anesthesia will be the first preference for most cardiac patients.

Recurrent Congenital Heart Diseases Among Neonates Born to Mothers with Congenital Heart Diseases.

The frequency of newborns with congenital heart disease (CHD) is approximately 1% in the general population; however, the recurrence rate of CHD in mothers with CHD differs in ethnicity and reports. We therefore aimed to determine the prevalence of CHD among neonates born to mothers with CHD in our institute in Japan. We reviewed the medical charts of 803 neonates delivered by 529 women with CHD at the National Cerebral and Cardiovascular Center from 1982 to 2016. They included isolated ventricular septal defect (VSD,31.4%), isolated atrial septal defect (ASD, 23.3%), tetralogy of Fallot (TOF,10.6%). We defined CHD in neonates as being diagnosed within 1 month of birth. We estimated that the average rate of the CHD recurrence was 3.1%. The recurrence ratios in each maternal CHD were 8.6%, 7.1%, 6.2%, 4.8%, 3.6%, and 1.5% for PS, CoA, TOF, atrioventricular septal defect, VSD, and ASD, respectively. The rate of CHD in offsprings whose mothers have CHD was 3 times greater than that of mothers with healthy hearts. Almost half of neonates with CHD had the same phenotype as their mother in our series. Especially, PS and CoA were closely related to the type of maternal CHD.

Utility of Fluid Assessment Based on the Intrathoracic Impedance Monitoring in a Peripartum Woman with Heart Disease.

Recently, implantable cardioverter-defibrillators (ICD) have become capable of monitoring intrathoracic impedance to detect an increased fluid volume and heart failure. Pregnancy is a well-known cause of an increased body fluid volume; however, it is not clear whether the measurement of intrathoracic impedance by ICD is clinically useful for precisely detecting heart failure in pregnant women. We herein report the case of a 39-year-old woman with an ICD that had been implanted after an event of ventricular fibrillation due to severe aortic regurgitation with a bicuspid aortic valve. Elevated right ventricular pressure and brain natriuretic peptide levels were detected at 37 weeks of gestation and postpartum. At the same time, the ICD's stored fluid index gradually increased and exceeded the threshold on the 10th day after delivery. She was treated with diuretics and recovered from postpartum heart failure. The physiological volume changed in the perinatal period, but we were still able to detect heart failure by ICD. Intrathoracic impedance monitoring is effective in the perinatal field.

Changes in echocardiographic parameters and hypertensive disorders in pregnancies of women with aortic coarctation.

OBJECTIVES: Pregnancy can be well tolerated after the repair of aortic coarctation. However, a higher incidence of hypertensive disorders during these pregnancies was reported. We analyzed the perinatal changes in echocardiographic parameters in women with aortic coarctation and investigated the risk factors of gestational hypertension (GH). METHODS: We retrospectively identified 15 pregnancies in nine Japanese women with aortic coarctation between 1982 and 2015. We categorized the patients according to the presence/absence of GH as the group with GH(n=3) and that without GH(n=12). The echocardiographic parameters were compared between groups. RESULTS: Our analysis revealed that a pre-pregnancy Doppler-measured pressure gradient≥20mmHg and a left ventricular mass index≥95g/m2 were significant risk factors for GH. The left ventricular end-diastolic diameters at the first and the third trimesters, the left ventricular end-systolic diameters at the first trimester, and the left ventricular ejection fraction at the third trimester were also significantly higher in the pregnancies with GH. All of these findings had been obtained before the patients' GH occurred. CONCLUSIONS: Hypertrophy of the left ventricle with a lower ejection fraction and a high pressure gradient across the coarctation were risk factors for GH in the patients with aortic coarctation. Thus, serial measurements using echocardiography are important for predicting GH in women with aortic coarctation. However, further research investigating this finding with a larger sample size is needed.

Intra- and post-partum acute aortic dissection (Stanford type B): Report of two cases.

Pregnancy with Marfan syndrome (MFS) presents challenges to the clinician because of the increased incidence of maternal cardiovascular complications, including acute aortic dissection (ADD) and the involvement of the fetus owing to the urgency of the need for surgery and the low likelihood of survival with premature delivery. Patient 1 was a 36-year-old pregnant Japanese woman with MFS who was referred at 16 gestational weeks with aortic root diameter 35.1 mm. Stanford type B AAD occurred on delivery without evident blood pressure changes. Patient 2 was a 31-year-old pregnant Japanese woman with MFS with aortic root diameter 28.3 mm at 20 gestational weeks after David procedure. Ultimately fatal Stanford type B AAD occurred on post-partum day 15. Both patients were treated with beta-blockers when AAD occurred. Although these two patients were initially considered to have relatively low risk according to previous reports and guidelines, AAD occurred. It is very important to provide information about these high pregnancy risks to women with MFS before conception, and to follow MFS pregnancies with great caution.

Beta-Blockers and Fetal Growth Restriction in Pregnant Women With Cardiovascular Disease.

BACKGROUND: The effects of ß-adrenergic blockers on the fetus are not well understood. We analyzed the maternal and neonatal outcomes of ß-adrenergic blocker treatment during pregnancy to identify the risk of fetal growth restriction (FGR). METHODS AND RESULTS: We retrospectively reviewed 158 pregnancies in women with cardiovascular disease at a single center. Maternal and neonatal outcomes were analyzed in 3 categories: the carvedilol (α/ß-adrenergic blocker; α/ß group, n=13); ß-adrenergic blocker (ß group, n=45), and control groups (n=100). Maternal outcome was not significantly different between the groups. FGR occurred in 1 patient (7%) in the α/ß group, in 12 (26%) in the ß group, and in 3 (3%) in the control group; there was a significant difference between the incidence of FGR between the ß group and control group (P<0.05). The ß group included propranolol (n=22), metoprolol (n=12), atenolol (n=6), and bisoprolol (n=5), and the individual incidence of FGR with these medications was 36%, 17%, 33%, and 0%, respectively. CONCLUSIONS: As a group, ß-adrenergic blockers were significantly associated with FGR, although the incidence of FGR varied with individual ß-blocker. Carvedilol, an α/ß-adrenergic blocker, had no association with FGR. More controlled studies are needed to fully establish such associations. (Circ J 2016; 80: 2221-2226).

Maternal and neonatal outcomes in labor and at delivery when long QT syndrome is present.

OBJECTIVE: Women during labor may be susceptible to torsades de pointes (TdP), which may cause the fetal condition to deteriorate. The aim of the present investigation was to analyze maternal and fetal outcomes during labor when long QT syndrome (LQTS) was present. METHODS: We examined the maternal and neonatal outcomes of 25 pregnancies (18 women) with LQT between 1995 and 2012 at the Department of Perinatology, National Cardiovascular Center, Japan. Maternal and neonatal outcomes including cardiovascular events, cardiovascular events within a week after delivery, caesarean delivery rate, still births, preterm births, and non-reassuring fetal heart rate pattern (NRFHR) during labor were investigated. RESULTS: All the mothers survived, and no cardiovascular events occurred in labor or postpartum due to LQTS in either vaginal delivery or caesarean delivery. A total of 23 women (92%) had used beta blockers in this study. Caesarean delivery was performed due to NRFHR during labor in 5 pregnancies (20%). CONCLUSION: Delivery when LQTS is present has a low likelihood of cardiovascular events, but pregnancy with LQTS had a higher caesarean delivery rate due to NRFHR in labor. Most women used beta blockers in this study, and it is possible that beta blocker use prevents cardiovascular events during labor. NRFHR during labor may be related with inherited LQT through the mother.

Depression of the apparent chiral recognition ability obtained in the host-guest complexation systems by electrospray and nano-electrospray ionization mass spectrometry.

Chiral recognition in the host-guest complexation systems of chiral crown ether hosts and amino ester guests was thoroughly examined using the electrospray ionization (ESI) mass spectrometry/enantiomer labeled (EL)-guest method. In this method, the mass spectra of a mixture of three components in a solution, a chiral host (H), an equal amount of an (S)-enantiomer guest labeled with deuterium atoms (G(S-dn)(+)) and an unlabeled (R)-enantiomer guest (G(R)+), were measured and the relative peak intensity value [I(H + G(R))(+) / I(H + G(S-dn))(+) = IRIS] of the host-guest complex ions, observed with an excess guest concentration, was taken to provide the chiral recognition ability of the host. In our earlier report (1996), we demonstrated that the apparent chiral recognition abilities using a mass spectrometer with a homemade ESI interface were depressed by about one tenth compared with the corresponding abilities obtained by fast-atom bombardment (FAB) MS. In the present study, the enantioselective complexation behaviors of various combinations of chiral crown hosts with chiral guests were further investigated in detail mainly using a modern commercial ESI/ion trap (IT) mass spectrometer. Consequently, it was found that the apparent IRIS values from the ESI-MS/EL-guest method changed significantly, depending upon the instrument used, and in particular, upon the ESI interfaces. Moreover, under the specific measuring conditions in ESI-IT-MS, the degrees of depression of the apparent chiral recognition abilities are roughly grouped into three classes, depending upon the number (or probably the type) of the hydrophobic substituents of the hosts. Representing the degrees by the slopes when plotting the apparent IRIS values in ESI-MS versus those in FAB-MS, the slopes for the three classes are (1) 1.0, (2) 0.7 and (3) 0.3; the higher the hydrophobicity of the hosts (and then, the host-guest complex ions), the lower the slope (the apparent enantioselectivity). Strengthening the degree of depression may be caused by an increase in the local concentration of the host close to the surface of the droplets produced during the electrospary ionization process. The chiral recognition ability (K(R )/ K(S)) in an equilibrated solution agrees quite well with the IRIS value in FAB-MS rather than that in ESI-MS.

New artificial host compounds containing galactose end groups for binding chiral organic amine guests: chiral discrimination and their complex structures.

New linear host (1) and cyclic hosts (2 and 3), which have galactopyranose skeletons as chiral origins and oxyethylenes skeletons as binding sites, were designed based on the structural features extracted from the fructo-oligosaccharide derivatives, having a large chiral discrimination ability, and were then synthesized. These hosts showed chiral discrimination toward chiral organic ammonium salts. For example, the chiral discrimination ability (the ratio of association constants: K(R)/K(S)) of host 1, which has the highest value among them, was K(R)/K(S) = 3 for Trp-O-(i)Pr(+) and K(R)/K(S) = 0.7 for 1-(1-naphthyl)ethylammonium (NEA(+)) at 298 K in CHCl(3). It was clarified that host 1 changed the conformation from a linear structure to the pseudo-ring structure by complexation with cations such as alkali metallic ions and chiral organic ammonium ions. The (1)H NMR induced shifts of host 1 by adding the NEA(+) guests showed that the host-guest complex structures are clearly different, depending upon the chirality of the guest; in the complex with (R)-NEA(+), the naphthyl group of the guest is located above the oxyethylene skeleton of the host and in the complex with (S)-NEA(+), and the naphthyl group is located between the edges of the pseudo-ring of the host. The clearly different structure of the complex of host 1 with NEA(+) may be caused by the dynamic molecular recognition, thus the induced-fitting mechanism.