Decreased Extracellular Vesicle Vasorin in Severe Preeclampsia Plasma Mediates Endothelial Dysfunction.

Background: Preeclampsia (PE) is a serious pregnancy complication affecting 5-8% of pregnancies globally. It is a leading cause of maternal and neonatal morbidity and mortality. Despite its prevalence, the underlying mechanisms of PE remain unclear. This study aimed to determine the potential role of vasorin (VASN) in PE pathogenesis by investigating its levels in extracellular vesicles (EV) and its effects on vascular function. Methods & Results: We conducted unbiased proteomics on urine-derived EV from severe PE (sPE) and normotensive pregnant women (NTP), identifying differential protein abundances. Out of one hundred and twenty proteins with ≥ ±1.5-fold regulation at P<0.05 between sPE and NTP, we focused on Vasorin (VASN), which is downregulated in sPE in urinary EV, in plasma EV and in the placenta and is a known regulator of vascular function. We generated EV with high VASN content from both human and murine placenta explants (Plex EV), which recapitulated disease-state-dependent effects on vascular function observed when treating murine aorta rings (MAR) or human aortic endothelial cells (HAEC) with murine or human plasma-derived EV. In normal murine pregnancy, VASN increases with gestational age (GA), and VASN is decreased in plasma EV, in placenta tissue and in Plex EV after intravenous administration of adenovirus encoding short FMS-like tyrosine kinase 1 (sFLT-1), a murine model of PE (murine-PE). VASN is decreased in plasma EV, in placenta tissue and in EV isolated from conditioned media collected from placenta explants (Plex EV) in patients with sPE as compared to NTP. Human sPE and murine-PE plasma EV and Plex EV impair migration, tube formation, and induces apoptosis in human aortic endothelial cells (HAEC) and inhibit acetylcholine-induced vasorelaxation in murine vascular rings (MAR). VASN over-expression counteracts the effects of sPE EV treatment in HAEC and MAR. RNA sequencing revealed that over-expression or knock down of VASN in HAEC results in contrasting effects on transcript levels of hundreds of genes associated with vasculogenesis, endothelial cell proliferation, migration and apoptosis. Conclusions: The data suggest that VASN, delivered to the endothelium via EV, regulates vascular function and that the loss of EV VASN may be one of the mechanistic drivers of PE. CLINICAL PERSPECTIVE: What is NewVASN in circulating plasma EV in sPE is reduced compared with VASN content in plasma EV of gestational age-matched pregnant women.VASN is encapsulated and transported in EV and plays a pro-angiogenic role during pregnancy.VASN should be explored both for its pro-angiogenic mechanistic role and as a novel biomarker and potential predictive diagnostic marker for the onset and severity of PE.What Are the Clinical Implications?VASN plays a role in maintaining vascular health and the normal adaptive cardiovascular response in pregnancy. A decrease of VASN is observed in sPE patients contributing to cardiovascular maladaptation.Strategies to boost diminished VASN levels and/or to pharmacologically manipulate mechanisms downstream of VASN may be explored for potential therapeutic benefit in PE.The decrease in EV-associated VASN could potentially be used as a (predictive) biomarker for PE.

Human Papillomavirus Types and Cervical Cancer Screening among Female Sex Workers in Cameroon.

BACKGROUND: Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including infection with human papillomavirus (HPV) and cervical cancer due to occupational exposure. The objective of this study was to estimate the prevalence of HPV, HPV types, and precancerous lesions of the cervix among FSWs in Cameroon. MATERIAL AND METHODS: In this cross-sectional study, FSWs in Cameroon aged 30 years and above were screened for cervical cancer using high-risk HPV testing and genotyping and visual inspection with acetic acid and Lugol's iodine (VIA/VILI) enhanced using digital cervicography (DC) simultaneously. Those who were positive for VIA/VILI-DC were provided treatment with thermal ablation (TA) immediately for cryotherapy/TA-eligible lesions while lesions meeting the criteria for large loop excision of the transformation zone (LLETZ) were scheduled at an appropriate facility for the LLETZ procedure. HPV-positive FSWs without any visible lesion on VIA/VILI-DC were administered TA. Bivariate analyses were conducted to compare demographic and clinical characteristics. Crude and adjusted logistic regression models were computed for HPV infection status and treatment uptake as outcomes in separate models and their ORs and 95% confidence intervals (95% CI) were reported. RESULTS: Among the 599 FSWs aged 30 years and older that were screened for HPV and VIA/VILI-DC, 62.1% (95% CI: (0.58-0.66)) were positive for one or more HPV types. HPV type 51 had the highest prevalence (14%), followed by types 53 (12.4%) and 52 (12.2%). Type 18 had the lowest prevalence of 2.8% followed by type 16 with 5.2%. In the multivariable model, HIV-positive FSWs were 1.65 times more likely to be infected with HPV compared to their HIV-negative counterparts (AOR: 1.65, CI: 1.11-2.45). A total of 9.9% of the 599 FSWs were positive for VIA/VILI-DC. CONCLUSION: The prevalence of HPV infection among FSWs in Cameroon is higher than the worldwide pooled FSW prevalence. HPV types 51 and 53 were the most prevalent, while types 18 and 16 were the least prevalent. HIV status was the only variable that was significantly associated with infection with HPV.

Analytical approaches to evaluating hypertensive disorders of pregnancy.

BACKGROUND: Data from the A Randomized Trial of Induction Versus Expectant Management study suggested that low-risk pregnant patients randomized to expectant management at term had a higher risk for developing hypertensive disorders of pregnancy than pregnant patients randomized to elective induction at 39 weeks. In addition, hypertensive disorders of pregnancy were reported to decrease with advancing gestational age when comparing outcomes by gestational age at delivery. OBJECTIVE: This study aimed to verify these contrasting findings by evaluating the relationship between hypertensive disorders of pregnancy at term and gestational age at delivery. STUDY DESIGN: This was a secondary analysis of a multicenter, prospective cohort study of nulliparous pregnant patients with singleton gestations (from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be). Pregnant patients who delivered ≥37+0 weeks' gestation were included. Patients were excluded if they did not provide consent for data release in subsequent studies or if they had missing outcome data. The primary outcome was hypertensive disorders of pregnancy, defined as gestational hypertension or preeclampsia with or without severe features according to the American College of Obstetricians and Gynecologists guidelines. Descriptive statistics were used to evaluate hypertensive disorders of pregnancy in the following 2 ways: analysis (1), incidence of hypertensive disorders of pregnancy by gestational age week among all ongoing pregnancies and analysis (2), the incidence of hypertensive disorders of pregnancy by gestational age week among deliveries at that gestational age week. It was assumed that hypertensive disorders of pregnancy were not expectantly managed at term. RESULTS: Of the 8011 pregnant patients included in this analysis, 1003 (12.5%) had hypertensive disorders of pregnancy: 162 (24.5%) delivered at 37+0 to 37+6 weeks' gestation, 232 (18%) delivered at 38+0 to 38+6 weeks, 310 (12.1%) delivered at 39+0 to 39+6 weeks, 207 (8.7%) delivered at 40+0 to 40+6 weeks, and 92 (8.1%) delivered at ≥41+0 weeks. In analysis 1, the incidence of hypertensive disorders of pregnancy increased with advancing gestational age among all ongoing pregnancies with a hypertensive disorder of pregnancy (2.0% at 37 weeks and 8.1% at 41 weeks). In analysis 2, the incidence of hypertensive disorders of pregnancy decreased with advancing gestational age among deliveries at that gestational age week alone (24.5% at 37 weeks and 8.1% at 41 weeks). CONCLUSION: Our results confirm the findings from the A Randomized Trial of Induction Versus Expectant Management study showing that the risk for hypertensive disorders of pregnancy increases with advancing gestational age, but hypertensive disorders of pregnancy is more common among deliveries at earlier gestational ages. These key differences illustrate how important the study design and analytical approach are to accurately interpret results and apply findings clinically.

Noninvasive Assessment of Right Ventricle Function and Pulmonary Artery Pressure Using Transthoracic Echocardiography in Women With Pre-Eclampsia: An Exploratory Study.

Background and objective Pre-eclampsia (PEC) is associated with the release of anti-angiogenic factors that are incriminated in raising systemic and pulmonary vascular resistance (PVR). Compared to the left heart and systemic circulation, much less attention has been paid to the right heart and pulmonary circulation in patients with PEC. We used transthoracic echocardiography (TTE) to estimate pulmonary artery (PA) pressure and right ventricular (RV) function in women with PEC. Materials and methods We conducted a case-control study at a tertiary care academic center. Ten early PEC (<34-week gestation) and nine late PEC (≥34-week gestation) patients with 11 early and 10 late gestational age-matched controls were enrolled. Two-dimensional TTE was performed on all patients. The estimated mean PA pressure (eMPAP) was calculated based on PA acceleration time (PAAT). PVR was estimated from eMPAP and RV cardiac output (RV CO). RV myocardial performance index (RV MPI), tricuspid annular plane systolic excursion (TAPSE), tissue tricuspid annular displacement (TTAD), and lateral tricuspid annular tissue peak systolic velocity (S') were measured. Results Compared to early controls, in early PEC, the eMPAP and estimated PVR (ePVR) were elevated, PAAT was reduced, RV MPI was increased, TTAD was reduced, and TAPSE and TV S' were unchanged. Compared to late controls, in late PEC, the eMPAP and ePVR were elevated, PAAT was reduced, and RV MPI was increased, while TAPSE, TTAD, and TV S' were unchanged. Conclusions In a sample of women with PEC, early PEC was found to be associated with increased eMPAP and ePVR and subclinical decrement of RV function as assessed by TTE. TTE may be a useful noninvasive screening tool for early detection of pulmonary hypertension and RV dysfunction in PEC. An adequately powered longitudinal study is needed to determine the implications of these findings on long-term outcomes.