Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

Background: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction.

Methods: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies.

Placental Mitochondrial Abnormalities in Preeclampsia.

Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission.

Hypoxia-induced mitochondrial abnormalities in cells of the placenta.

Introduction: Impaired utero-placental perfusion is a well-known feature of early preeclampsia and is associated with placental hypoxia and oxidative stress. Although aberrations at the level of the mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to placental oxidative stress is unknown.

Methods: We explored whether abnormalities in mitochondrial metabolism contribute to hypoxia-induced placental oxidative stress by using both healthy term placentae as well as a trophoblast cell line (BeWo cells) exposed to hypoxia.

NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype.

Hypertension is the most important cause of death and disability in the elderly. In 9 out of 10 cases, the molecular cause, however, is unknown. One mechanistic hypothesis involves impaired endothelium-dependent vasodilation through reactive oxygen species (ROS) formation.

Placental hypoxia-induced alterations in vascular function, morphology, and endothelial barrier integrity.

Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension and proteinuria that affects 3-10% of all pregnancies. Although its pathophysiology remains obscure, placental hypoxia-induced oxidative stress and alterations in vascular function, morphology, and endothelial barrier integrity are considered to play a key role in the development of preeclampsia. In this study, placental villous explants of noncomplicated placentae and BeWo cells were subjected to hypoxia.

The direct and sustained consequences of severe placental hypoxia on vascular contractility.

Introduction: Preeclampsia is a major health problem in human pregnancy, severely complicating 5-8% of all pregnancies. The emerging molecular mechanism is that conditions like hypoxic stress trigger the release of placental messengers into the maternal circulation, which causes preeclampsia. Our objective was to develop an in vitro model, which can be used to further elucidate the molecular mechanisms of preeclampsia and which might be used to find a remedy.

Co-constructed health narratives during a 'media event': The case of the first Dutch Twitter heart operation.

Objective: This article examines the relationship between microblogging and the development of health narrative through the lens of an institution-initiated media event, the first live-tweeted heart operation in the Netherlands. It specifically addresses the question, how does health narrative take shape on a microblog and other (social) media, through the combination of self-initiated status updates, reactions to questions and short conversations with followers?

Methods: A combination of qualitative and quantitative data analysis was used to identify prominent themes in the tweets and trace the complex process by which the narrative took shape. The results presented here are derived from the qualitative analysis.

Cerebral Artery Vasoconstriction is Endothelin-1 Dependent Requiring Neurogenic and Adrenergic Crosstalk.

Background: The regulation of cerebral arterial vasomotor tone involves several mechanisms. The role of sympathetic nerves and the adrenergic neurotransmitter, noradrenaline (NA), has been the subject of debate for decades. Moreover, the specific role of endothelin-1 (ET-1) in cerebral arterial vasoconstriction has not been elucidated to date.

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR.

Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR).

Rutin protects against HO-triggered impaired relaxation of placental arterioles and induces Nrf2-mediated adaptation in Human Umbilical Vein Endothelial Cells exposed to oxidative stress.

Background: Rutin intake is associated with a reduced risk of cardiovascular disease (CVD). The exact mechanism by which rutin can protect against CVD development is still enigmatic. Since, rutin is a compound with a relatively short half-life, the direct antioxidant effect of rutin cannot explain the long-lasting effect on human health.

Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis.

Limited literature sources implicate mast-cell mediator chymase in the pathologies of pulmonary hypertension and pulmonary fibrosis. However, there is no evidence on the contribution of chymase to the development of pulmonary hypertension associated with lung fibrosis, which is an important medical condition linked with increased mortality of patients who already suffer from a life-threatening interstitial lung disease.The aim of this study was to investigate the role of chymase in this particular pulmonary hypertension form, by using a bleomycin-induced pulmonary hypertension model.

The supplement-drug interaction of quercetin with tamsulosin on vasorelaxation.

The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade.

Imaging evidence for endothelin ETA/ETB receptor heterodimers in isolated rat mesenteric resistance arteries.

Aims: In engineered cells, endothelin ETA and ETB receptors can heterodimerize. We tested whether this can also be observed in native tissue.

Main Methods: Rat mesenteric resistance arteries (rMRA) were maintained in organ culture for 24h to upregulate ETB-mediated contractions in addition to their normal ETA-mediated responses.

Increasing girls' knowledge about human papillomavirus vaccination with a pre-test and a national leaflet: a quasi-experimental study.

Background: Adolescent girls are at an age to be involved in the decision about HPV vaccination uptake and therefore need adequate information about the vaccination. This study assesses to what extent reading an official information leaflet about HPV contributes to girls' knowledge levels, and to what extent an increase in knowledge is boosted by a pre-test measurement.

Methods: Participants (girls aged 11-14 years) were systematically allocated to group A that completed a pre-test measurement (12 true/false statements) or to group B that did not complete it.

Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats.

Background: Endothelin-1 (ET1) is a potent vasoconstrictor peptide with pro-mitogenic and pro-inflammatory properties and is therefore of interest in the development of endothelial dysfunction, endothelium-dependent flow-related remodeling, and hypertension-related remodeling. ET1 can be formed through cleavage of big ET1 by endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP).

Method: We investigated whether the dual NEP/ECE inhibitor SOL1 improves resistance artery function and structure in 12 weeks old spontaneously hypertensive rats (SHRs) and whether arterial structural responses to decreased (-90%) or increased (+100%) blood flow are impaired in young SHRs.

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats.

Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks.

Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats.

We tested the hypotheses that TSP-1 participates in the initiation of remodeling of small muscular arteries in response to altered blood flow and that the N-terminal domain of TSP-1 (hepI) can reverse the pathological inward remodeling of resistance arteries from SHR.We measured (1) changes in gene/protein expression in MA of 6 week old WKY and SHR exposed to either increased (+ 100 %) or reduced blood flow (- 90 %) for 24-40 hours and (2) structural changes in MA of 12 week old SHR exposed for 3 days to hepI in organ culture.In both HF and LF of WKY, mRNA expression of eNOS, sGCα1 and PKG1β were significantly reduced (p < 0.

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease.

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial.

NOX1, 2, 4, 5: counting out oxidative stress.

For decades, oxidative stress has been discussed as a key mechanism of endothelial dysfunction and cardiovascular disease. However, attempts to validate and exploit this hypothesis clinically by supplementing antioxidants have failed. Nevertheless, this does not disprove the oxidative stress hypothesis.

Genetic variation in the renin--angiotensin system, use of renin--angiotensin system inhibitors and the risk of myocardial infarction.

Introduction: This study investigated whether variation in the genes encoding for ACE, AGT and AGTR1 modifies the risk of myocardial infarction (MI) related to ACE inhibitors and AT II antagonists.

Methods: A nested case-control study among users of antihypertensive drugs, in whom the polymorphisms ACE-G4656C, ACE-T3892C, AGT-C235T and AGTR1-A1166C were genotyped.

Results: Among 613 cases and 3630 controls, the risk of MI was significantly lower among users of ACE inhibitors compared with that in users of other antihypertensives (adjusted OR, 0.

Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery.

Background: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown.

Methods And Results: Here, we report that VEGF( partial differential/ partial differential) mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries.

Telomere length and its associations with oxidized-LDL, carotid artery distensibility and smoking.

Oxidative stress is a key factor driving the aging of cells and arteries. Studies suggest that white blood cell (WBC) telomere length is an index of systemic aging. We, therefore, investigated the association between WBC telomere length and oxidized-LDL, and vascular aging, expressed by the distensibility of the carotid artery.

Determinants of DNA yield and purity collected with buccal cell samples.

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed.

Renin-angiotensin system polymorphisms and the association between use of angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors and the risk of diabetes.

Introduction: We assessed the influence of genetic polymorphisms in the renin-angiotensin system on the risk of diabetes associated with the use of angiotensin II receptor blockers and angiotensin-converting enzyme (ACE) inhibitors.

Materials And Methods: We performed a matched case-control study among antihypertensive drug users. Pharmacy records and questionnaires were used to ascertain incident diabetes (cases), antihypertensive drug use, and risk factors.

Reasons for non-response in observational pharmacogenetic research.

Purpose: In epidemiological studies, non-response may introduce bias and limit generalizability. In genetic pharmacoepidemiological research, collection of DNA might be a major reason for non-response. We determined reasons for non-response and compared characteristics of non-responders and responders in a pharmacogenetic case-control study.