65: Maternal obesity programs offspring hypertension via adipose renin-angiotensin system

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    www.AJOG.org Hypertension/Physiology Oral Concurrent Session 6t this trend was not significant in males (nicotine, n6; control,9). Sucrose intake, total cholesterol, low-/very low-density lipo-teins and triglyceride concentrations were similar between groups

    both males and females. Both nicotine-exposed males and femalessignificantly lower high-density lipoprotein (HDL) concentra-

    ns than their control counterparts (males: 75.8 /3.9 vs. 92.7 4.1 ng/dL; females: 60.9/ 2.2 vs. 75.3/ 3.8 ng/dL).NCLUSION: Perinatal nicotine exposure is associated with signifi-tly decreased HDL cholesterol levels in both male and female off-ing, and this effect is independent of adiposity and feeding pat-ns. These findings provide further evidence that female offspringosed to nicotine during perinatal development are at increased riskcardiovascular disease compared to controls.

    Maternal obesity programs offspring hypertensionadipose renin-angiotensin system

    istiane Guberman1, Guang Han1, Michael Ross1, Mina Desai1

    BioMed at Harbor-UCLA Med. Ctr., Obstetrics and Gynecology,rance, CA

    JECTIVE: Maternal obesity programs an increased risk of offspringesity and systemic hypertension. Although renal renin-angiotensintem (RAS) is known to regulate blood pressure, it is now recog-ed that RAS is also activated in adipose tissue during obesity. An-tensinogen (AGT) is the only known precursor of the vasoactivetide angiotensin II (AngII), which mediates vasopressor effects viatype 1 receptor (AT1). We hypothesized that programmed off-ing hypertension is dependent upon enhanced adipose tissue RASoffspring of obese rat dams.DY DESIGN: At 3 week of age, female rats were weaned to high fat

    F: 60% k/cal) or (control, 10% k/cal) diet. At 11 weeks of age, theses were mated and continued on their respective diets during preg-cy. After birth, litter size was standardized, pups cross-fostered totrol dams and weaned to normal diet. At 6 months of age, body fat

    EXA) and blood pressure (tail-cuff) were measured. Thereafter,cutaneous and retroperitoneal adipose tissue was harvested fromle offspring. Protein expression (Western Blot) of AGT and AT1s determined and normalized values presented as fold change.ULTS: At 1 day and 6 months of age, HF had comparable body

    ights, but markedly increased body fat (263 vs 182 %) andod pressure (1484 vs 1354 mm Hg) as compared to Controls.analysis of adipose tissue, HF offspring demonstrated significantlyreased AGT (4-fold) and AT1 (6-fold) expression in retroperito-l, though not subcutaneous adipose tissue.

    NCLUSION: Despite having comparable body weights, offspring of-fed dams are obese, hypertensive and exhibit upregulated retro-itoneal adipose AGT and AT1. These findings suggest that pro-

    concentration (ng/dL) in control vs. nicotine-exposed male (left panel) and female (right panel)pring.mmed adiposity and adipose tissue enhanced RAS may contributehypertension in offspring of obese/HF dams.

    SupplemenMicroRNA expression profiles in firstester trophoblast of pregnancies

    stined to develop severe preeclampsiaishna Singh1, Lindsay Spurka2, Jordon Brown2,cent Funari3, Siegfried Rotmensch4

    dars-Sinai Medical Center, Division of Maternal-Fetal Medicine,partment of Obstetrics and Gynecology, Los Angeles, CA, 2Medical

    etics Institute at Cedars-Sinai Medical Center, Genomics Core, Losgeles, CA, 3Cedars-Sinai Medical Genetics Institute, David Geffen School

    edicine at UCLA, Division of Medical Genetics and Biomedical Sciences,partment of Pediatrics, Los Angeles, CA, 4Cedars-Sinai Medical Center,vid Geffen School of Medicine at UCLA, Division of Maternal-Fetaldicine, Department of Obstetrics and Gynecology, Los Angeles, CAJECTIVE: Studies on 1st trimester trophoblast suggest differentiale expression in severe preeclampsia (SP). MicroRNAs (miRNA)dulate gene expression and unique signatures have been identifiedplacental trophoblast at advanced gestations. We examinedether miRNA is differentially expressed in first trimester tropho-st of pregnancies destined to develop severe preeclampsia.DY DESIGN: 1st trimester trophoblast was prospectively collected

    m women undergoing CVS at 10-13 wks gestation for prenatal diag-sis. Samples were stored in RNAlater at -80 C. Clinical informations obtained from designated patient questionnaires and medical re-ds. SP was diagnosed by ACOG criteria. Singleton SP cases (n5) andrmal controls (n5) were matched for maternal age, ethnicity, parity,tational age at CVS, and fetal sex (only females) and comorbiditiesre excluded. Each RNA sample was processed with the FlashTa BiotinR RNA Labeling Kit For Affymetrix GeneChip miRNA Arrays andre hybridized to GeneChip miRNA 3.0 Arrays. miRNA expression wasrmalized and then analyzed using Expression Console with RMA BG respectively.ULTS: Mean gestational age at delivery was 36.9wks (range 29.0.0wks) and 39.6wks (range37.4-40.4 wks) for SP and normal controls,pectively. Principal component analysis revealed that most of the mo-ular signatures are similar (Figure). Of the 1438 miRNAs analyzed, 576re expressed in controls vs. 588 in SP. Supervised analysis of mi-RNAression including a 2-way Wilcoxon T-Test showed that 24 miRNAssignificantly upregulated among SP vs controls, 5 with 1.5 foldnge. Some of the upregulated mi-RNAs regulate matrix metallopro-ases and genes for apoptosis, cellular movement and growth.

    NCLUSION: 1st trimester trophoblast from pregnancies destined toelop SP display differential expression of miRNAs, which may be

    trumental in the pathophysiology of SP by affecting trophoblastasion into the placental bed.t to JANUARY 2013 American Journal of Obstetrics& Gynecology S39


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