Circulating vascular endothelial growth factor receptor-3, a pro-lymphangiogenic and pro-angiogenic mediator, is decreased in pre-eclampsia.

Objective: To compare circulating levels of vascular endothelial growth factor receptor 3 (VEGFR-3) in women with pregnancy-induced hypertension (PIH) and in non-pregnant (NP) and healthy pregnant (HP) women.

Methods: We conducted a case-control study including PIH (n = 135), HP (n = 68), and NP (n = 49) women from southeastern Brazil. PIH were diagnosed according to international guidelines, and defined as gestational hypertension (GH, n = 61) or pre-eclampsia (n = 74).

Sex differences in metabolic adaptation in infants with cyanotic congenital heart disease.

Background: Female infants with congenital heart disease (CHD) face significantly higher postoperative mortality rates after adjusting for cardiac complexity. Sex differences in metabolic adaptation to cardiac stressors may be an early contributor to cardiac dysfunction. In adult diseases, hypoxic/ischemic cardiomyocytes undergo a cardioprotective metabolic shift from oxidative phosphorylation to glycolysis which appears to be regulated in a sexually dimorphic manner.

Functional polymorphisms of and affect both nitric oxide formation and association with hypertensive disorders of pregnancy.

Impaired nitric oxide (NO) formation may be associated with endothelial dysfunction and increased cardiovascular disease risk in preeclampsia (PE). Functional single-nucleotide polymorphisms (SNPs) of nitric oxide synthase 3 () (rs3918226) and guanylate cyclase 1, soluble, alpha 3 () (rs7692387) increase susceptibility to the adverse consequences due to inadequate generation of NO by the endothelium. However, no previous study has examined whether these SNPs affect NO formation in healthy pregnancy and in gestational hypertension (GH) and PE.

Increased platelet mitochondrial function correlates with clot strength in a rodent fracture model.

Background: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function but has not yet been correlated with functional coagulation studies.

Circulating levels of tissue inhibitor of metalloproteinase 3, a protein with inhibitory effects on angiogenesis, are increased in pre-eclampsia.

Objective: To assess and compare circulating tissue inhibitor of metalloproteinase 3 (TIMP-3) concentrations between women with pre-eclampsia and healthy pregnant women. We also aimed to determine the relationships between circulating TIMP-3 and matrix metalloproteinase 2 (MMP-2), MMP-9, TIMP-1, and TIMP-2 concentrations in pre-eclampsia.

Methods: A primary case-control study included patients with pre-eclampsia (n = 219) and gestational hypertension (n = 118), healthy pregnant women (n = 214), and non-pregnant women (n = 66), and a replication case-control study included patients with pre-eclampsia (n = 177) and healthy pregnant women (n = 124), all from southeastern Brazil.

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction.

Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved.

Placental Ischemia Says "NO" to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia.

In this review, we first provide a brief overview of the nitric oxide synthase (NOS) isoforms and biochemistry. This is followed by describing what is known about NOS-mediated blood pressure control during normal pregnancy. Circulating nitric oxide (NO) bioavailability has been assessed by measuring its metabolites, nitrite (NO) and/or nitrate (NO), and shown to rise throughout normal pregnancy in humans and rats and decline postpartum.

Circulating levels of hydrogen sulphide negatively correlate to nitrite levels in gestational hypertensive and preeclamptic pregnant women.

Endothelial dysfunction is a hallmark of preeclampsia and the role of nitric oxide (NO) has been extensively studied in this pregnancy complication. In recent years, hydrogen sulphide (H S) has arisen as a new gasotransmitter with an impact on endothelial function. However, the involvement of H S in the pathophysiology of preeclampsia is not fully understood, and only a few studies with limited sample size have investigated circulating levels of H S in preeclamptic patients.

single-nucleotide polymorphism rs1319501 and visfatin/NAMPT affect nitric oxide formation, sFlt-1 and antihypertensive therapy response in preeclampsia.

We examined the relationships between visfatin/NAMPT and nitrite concentrations (a marker of nitric oxide [NO] formation) or sFlt-1 levels in 205 patients with preeclampsia (PE) responsive or nonresponsive to antihypertensive therapy, and whether SNPs rs1319501 and rs3801266 affect nitrite concentrations in PE and 206 healthy pregnant women. Circulating visfatin/NAMPT and sFlt-1 levels were measured by ELISA, and nitrite concentrations by using an ozone-based chemiluminescence assay. In nonresponsive PE patients, visfatin/NAMPT levels were inversely related to nitrite concentrations and positively related to sFlt-1 levels.

Impact of hyperleptinemia during placental ischemia-induced hypertension in pregnant rats.

The prevalence of preeclampsia and obesity have increased. Although obesity is a major risk factor for preeclampsia, the mechanisms linking these morbidities are poorly understood. Circulating leptin levels increase in proportion to fat mass.

Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes.

Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE).

Chronic CNS-mediated cardiometabolic actions of leptin: potential role of sex differences.

Previous studies using male rodents showed the adipocyte-derived hormone leptin acts in the brain to regulate cardiovascular function, energy balance, and glucose homeostasis. The importance of sex differences in cardiometabolic responses to leptin, however, is still unclear. We examined potential sex differences in leptin's chronic central nervous system (CNS)-mediated actions on blood pressure (BP), heart rate (HR), appetite, and glucose homeostasis in normal and type 1 diabetic rats.

A rat model of orthopedic injury-induced hypercoagulability and fibrinolytic shutdown.

Background: Postinjury hypercoagulability occurs in >25% of injured patients, increasing risk of thromboembolic complications despite chemoprophylaxis. However, few clinically relevant animal models of posttraumatic hypercoagulability exist. We aimed to evaluate a rodent model of bilateral hindlimb injury as a preclinical model of postinjury hypercoagulability.

Administration of recombinant human placental growth factor decreases blood pressure in obese hypertensive pregnant rats.

Objectives: Although epidemiological studies have shown that obesity is associated with increased incidence of hypertension during pregnancy, the mechanisms linking these two comorbidities are not as well studied. Previous investigations detected lower levels of the anti-hypertensive and pregnancy-related factor, placental growth factor (PlGF), in obese hypertensive pregnancies. Therefore, we examined whether obese hypertensive pregnant rats have reduced PlGF and whether increasing its levels by administering recombinant human (rh)PlGF reduces their blood pressure.

Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats.

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension linked to placental ischemia. While obesity is a major risk factor for preeclampsia, not all obese pregnant women develop pregnancy-induced hypertension or preeclampsia. Previously, we reported that placental ischemia-induced hypertension is dependent upon intact signaling of the sympathetic nervous system.

Circulating Tissue Inhibitor of Metalloproteinase-4 levels are not a Predictor of Preeclampsia in the period between 20 and 25 Weeks of Gestation.

Objective:  To evaluate whether the circulating level of tissue inhibitor of metalloproteinase-4 (TIMP-4) in the period between 20 and 25 weeks of gestation is a predictor of preeclampsia.

Methods:  We have performed a case-control study, nested in a prospective study cohort in Ribeirão Preto, in the state of São Paulo, Brazil. Of the 1,400 pregnant women evaluated between 20 and 25 weeks of gestation, 460 delivered in hospitals outside of our institution.

Role of Nitric Oxide Synthase on Blood Pressure Regulation and Vascular Function in Pregnant Rats on a High-Fat Diet.

Background: While obesity is a leading risk factor for preeclampsia, the mechanisms whereby obese women are more susceptible to pregnancy-induced hypertension are unclear. As high-fat diet (HFD) is an important contributor to the development of obesity, we tested the hypothesis that pregnant rats on HFD have hypertension and endothelial dysfunction due to reduced nitric oxide synthase (NOS).

Methods: Twelve-week-old Sprague-Dawley female rats were fed normal diet (ND, 13% fat kcal) or HFD (40% fat kcal) for 9 weeks.

Pharmacogenetics in the treatment of pre-eclampsia: current findings, challenges and perspectives.

Pre-eclampsia (PE) is defined as pregnancy-induced hypertension and proteinuria, and is a major cause of maternal and perinatal morbidity and mortality. A large subgroup of pregnant women with PE is nonresponsive to antihypertensive drugs, including methyldopa, nifedipine and hydralazine. Pharmacogenomics may help to guide the individualized therapy for this nonresponsive subgroup.

Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats.

Objectives: Although obesity increases the risk for hypertensive disorders of pregnancy, the mechanisms remain unclear. Neural melanocortin-4 receptor (MC4R) deficiency causes hyperphagia and obesity. Effects of MC4R deficiency on body weight, blood pressure (BP) and placental inflammatory responses to high-fat diet (HFD) are unknown.