Linking placental ischemia and hypertension in preeclampsia: role of endothelin 1.

Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216, USA.
Hypertension (Impact Factor: 6.87). 05/2012; 60(2):507-11. DOI: 10.1161/HYPERTENSIONAHA.112.194845
Source: PubMed
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    ABSTRACT: Formerly preeclamptic women demonstrate higher prevalence of metabolic syndrome (MetS), impaired vascular function and increased sympathetic activity and are at increased risk of cardiovascular disease. The aim of this study was to assess the effects of 12-weeks exercise training (70-80%VO2max) in formerly preeclamptic women on physical fitness, components of metabolic syndrome, vasculature and autonomic functions compared to healthy controls. Prospective case-control study including 24 normotensive formerly preeclamptic women and 20 controls matched for age and post-partum interval (all 6-12 months postpartum). Before and after training, we measured all components of MetS (i.e. blood pressure, lipids, glucose/insulin and albuminuria), carotid intima-media thickness (IMT) and brachial (BA) and superficial femoral artery (SFA) endothelial function using flow mediated dilation (FMD). Autonomic activity was quantified using power spectral analysis (Low Frequency/High Frequency power (LF/HF)-ratio). At baseline, formerly preeclamptic women demonstrated higher values of most components of MetS. Compared to controls, formerly preeclamptic women had increased IMT (580±92μm vs. 477±65 μm), impaired endothelial function (FMD BA:5.3±2.2% vs. 10.8±3.5% and FMD SFA:4.9±2.1% vs. 8.7±3.2%) and increased LF/HF-ratio (2.2±1.0 vs. 1.3±0.4, all p<0.05). In both groups exercise training decreased values of most components of MetS and IMT, improved FMD and concurrently reduced LF/HF. Despite these improvements, vascular and autonomic variables did not normalize by 12 weeks training in formerly preeclamptic women. This study demonstrates that exercise training in formerly preeclamptic women and controls improves components of MetS, endothelial function, vascular wall thickness and autonomic control. Nonetheless, trained formerly preeclamptic women only reached a cardiovascular status that is comparable to sedentary healthy controls. Registration number: NCT00900458
    American journal of obstetrics and gynecology 04/2014; · 3.28 Impact Factor
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    ABSTRACT: Abstract Objective: α-klotho, a protein with anti-aging properties, has been involved in important biological processes, such as calcium/phosphate metabolism, resistance to oxidative stress, and nitric oxide production in the endothelium. Recent studies have suggested a role of α-klotho in endocrine regulation of mineral metabolism and postnatal growth in infants. Yet, the role of α-klotho during pregnancy remains largely unknown. The aim of this study was to determine whether maternal plasma concentration of α-klotho change during pregnancy and evaluate its expression in pregnancies complicated by preeclampsia with or without small for gestational age (SGA) neonate. Study design: This cross-sectional study included patients in the following groups: (1) non pregnant women (n = 37); (2) uncomplicated pregnancy (n = 130); (3) preeclampsia with an appropriate weight for gestational age (AGA) neonate (PE; n = 58); (4) preeclampsia with an SGA neonate (PE and SGA; n = 52); and (5) SGA neonate without preeclampsia (SGA; n = 52). Plasma concentrations of α-klotho were determined by ELISA. Results: The median plasma α-klotho concentration was higher in pregnant than in non-pregnant women. Among women with an uncomplicated pregnancy, the median plasma concentration of α-klotho increases as a function of gestational age (Spearman Rho = 0.2; p = 0.006). The median (interquartile range) plasma concentration of α-klotho in women with PE and SGA [947.6 (762 - 2013) pg/mL] and SGA without [1000 (585-1567) pg/mL] were 21% and 17% lower than that observed in women with an uncomplicated pregnancy [1206.6 (894-2012) pg/mL], (p= 0.005 and p = 0.02), respectively. Additionally, there were no significant differences in the median plasma concentration of α-klotho between uncomplicated pregnancies and women with PE who deliver an AGA neonate. Conclusion: Maternal plasma concentrations of α-klotho are higher during pregnancy than in a non-pregnant state. Moreover, the median maternal plasma concentration of α-klotho was lower among mothers who deliver an SGA neonate regardless of the presence or absence of preeclampsia than in those with an uncomplicated pregnancy.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 07/2013; · 1.36 Impact Factor
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    ABSTRACT: Objective: An animal model of hemolysis, elevated liver enzymes, low platelet count (HELLP) was used to determine if T lymphocytes accompany hypertension and increased inflammatory cytokines. Methods: sFlt-1 (4.7 µg/kg/day) and sEndoglin (7 µg/kg/day) were infused into normal pregnant rats (HELLP rats) for 8 days. Results: HELLP was associated with increased mean arterial pressure (p = 0.0001), hemolysis (p = 0.044), elevated liver enzymes (p = 0.027), and reduced platelets (p = 0.035). HELLP rats had increased plasma levels of TNFα (p = 0.039), IL-6 (p = 0.038) and IL-17 (p = 0.04). CD4(+) and CD8(+) T lymphocytes were increased. Conclusion: These data support the hypothesis that T cells are associated with hypertension and inflammation.
    Hypertension in Pregnancy 02/2014; 33(1):41-54. · 0.93 Impact Factor


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Aug 21, 2014