Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat

Banek, Christopher T.; Bauer, Ashley J.; Gingery, Anne; Gilbert, Jeffrey S.

doi:10.1152/ajpregu.00250.2012

Cited by 16 publications

(20 citation statements)

References 49 publications

(80 reference statements)

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“…The RUPP procedure is a robust model for studying the link between placental ischemia and hypertension in the pregnant rat and has been described in detail previously (3,17). In brief, silver clips were placed on the lower abdominal aorta (0.203-mm inner diameter) above the iliac bifurcation and also on branches (0.100 mm inner diameter) of both the right and left ovarian arteries supplying the uterus on day 14 of gestation (term ϭ 21 days).…”

Section: Methodsmentioning

confidence: 99%

“…After the measurement of MAP, the dams were placed under isoflurane anesthesia and a midline ventral incision was made to isolate the abdominal aorta for plasma and serum collection as reported previously (3,17). Blood was collected for subsequent assays into Corvac sterile serum separator tubes (Sherwood Davis, St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…Blood and amniotic fluid glucose concentrations were measured as reported previously (21). Fetal weight, placental weight, and number of resorptions were recorded in the manner described previously (3,17). All collected tissues for subsequent analysis were flash frozen in liquid nitrogen and stored at Ϫ80°C.…”

Section: Methodsmentioning

confidence: 99%

“…Plasma concentrations of free VEGF and sFlt-1 were measured using commercial enzyme linked immunosorbant assay kits (R&D Systems, Quantikine; Minneapolis, MN) according to the manufacturer's directions as described previously (3,17).…”

Section: Methodsmentioning

confidence: 99%

“…An imbalance favoring increased anti-angiogenic factors has been strongly linked to the etiology of hypertension during preeclampsia (3,18,27,29). Recent studies also indicate restoration of angiogenic balance can mitigate an increase in blood pressure observed in several rodent models of preeclampsia (17,18,27,28,37).…”

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AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat

Banek

Bauer

Needham

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Banek CT, Bauer AJ, Needham KM, Dreyer HC, Gilbert JS. AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat. Am J Physiol Heart Circ Physiol 304: H1159 -H1165, 2013. First published February 15, 2013 doi:10.1152/ajpheart.00903.2012.-Previous studies suggest restoration of angiogenic balance can lower blood pressure and improve vascular endothelium function in models of preeclampsia. Our laboratory has recently reported exercise training mitigates hypertension in an animal model of preeclampsia, but the mechanisms are unknown. AMP-activated protein kinase (AMPK) is stimulated during exercise and has been shown to increase expression of VEGF. Therefore, the purpose of this study was to determine whether AICAR (5-aminoimidazole-4-carboxamide-3-ribonucleoside), a potent AMPK stimulator, would increase circulating VEGF, improve angiogenic potential, decrease oxidative stress, and abrogate placental ischemia-induced hypertension. In rats, reduced uteroplacental perfusion pressure (RUPP) was induced on day 14 of gestation by introducing silver clips on the inferior abdominal aorta and ovarian arteries. AICAR was administered intraperitoneally (50 mg/kg b.i.d.) days 14 -18, and blood pressure and tissues were collected on day 19. RUPP-induced hypertension was ameliorated (P Ͻ 0.05) with AICAR versus RUPP. AICAR increased (P Ͻ 0.05) plasma VEGF and decreased (P Ͻ 0.05) plasma soluble VEGF receptor-1 in the RUPP ϩ AICAR versus RUPP. Antioxidant capacity was restored (P Ͻ 0.05) by AICAR in RUPP placenta. Renal and placental catalase activity was decreased (P Ͻ 0.05) in RUPP ϩ AICAR versus RUPP. Angiogenic potential was increased (P Ͻ 0.05) in RUPP ϩ AICAR versus RUPP. Fetal and placental weights were unaffected by AICAR. Placental AMPK phosphorylation was increased (P Ͻ 0.05) in RUPP ϩ AICAR versus normal pregnant and RUPP. These findings suggest AICAR may be useful to mitigate angiogenic imbalance, renal, and placental oxidative stress and increase in blood pressure associated with RUPP hypertension. Furthermore, placental AMPK phosphorylation was observed only in the setting of ischemia. preeclampsia; hypertension; angiogenic balance; 5-aminoimidazole-4-carboxamide-3-ribonucleoside PREECLAMPSIA, A pregnancy-specific syndrome, is the leading cause of fetal and maternal morbidity and mortality across the world, and unfortunately the incidence has been increasing in recent decades (32, 35). Currently, there are limited treatments available, and early delivery is often indicated to prevent further progression of the syndrome. Consequently, preeclampsia is the leading cause of premature delivery, which is well known to have numerous deleterious effects on neonatal and life-long health (32,35).Recent clinical and experimental studies suggest dysregulation of circulating angiogenic factors results in an angiogenic imbalance that is most notably characterized by an altered ratio of pro-angiogenic (e.g., VEGF) and anti-angiogenic factors (e.g., soluble VEGF receptor-1, or s...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat

Banek

Bauer

Needham

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Placental Disease and the Maternal Syndrome of Preeclampsia: Missing Links?

Tannetta

Sargent

2013

Curr Hypertens Rep

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Preeclampsia remains a significant obstetric risk worldwide. The pathophysiology of preeclampsia is complex, with multiple stages involving maladaptations in both placental and maternal physiology. The placenta links the pre-clinical stage of impaired remodeling of the uterine vasculature, occurring in early pregnancy, to the later clinical stages characterised by the maternal syndrome of hypertension and proteinuria. This review focuses on some of the recent candidates for the missing links in this process.

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Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia

Chaiworapongsa

Romero

Korzeniewski

et al. 2013

American Journal of Obstetrics and Gynecology

130

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OBJECTIVE To determine if maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30–34 weeks can identify mothers at risk for preeclampsia (PE), stillbirth and small-for-gestational-age neonates (SGA). STUDY DESIGN A prospective cohort study included 1269 singleton pregnant women who had blood samples obtained at 30–34 weeks and delivered after 34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by ELISA. RESULTS The prevalence of late (>34 weeks) PE, severe late PE, stillbirth and SGA was 3.2% (n=40), 1.8% (n=23), 0.4% (n=5) and 8.5% (n=108), respectively. A plasma concentration of PlGF/sEng <0.3 MoM was associated with severe late PE [adjusted odds ratio (aOR) 16]; addition of PlGF/sEng to clinical risk factors increased the area under the ROC curve (AUC) from 0.76 to 0.88 (p=0.03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20–25 weeks for the prediction of severe late PE (comparison of AUC; each p≤0.02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false positive rate of 15% for the identification of severe late PE. A plasma concentration of PlGF/sVEGFR-1 <0.12 MoM at 30–34 weeks had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80% and specificity 93%) were observed in a separate case-control study. Integrating these biomarkers with clinical data did not improve the prediction of SGA. CONCLUSIONS Risk assessment for severe late PE and stillbirth in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and anti-angiogenic factors at 30–34 weeks of gestation.

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Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat

Cited by 16 publications

References 49 publications

AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat

AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat

Placental Disease and the Maternal Syndrome of Preeclampsia: Missing Links?

Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia

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