45: effect of high fat diet on metabolic programming in offspring born to hypertensive mother

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Friday, February 6, 2015 d 1:15 pm e 3:30 pm d Indigo BF HYPERTENSION Abstracts 44 e 52 Moderators: Virginia Winn, MD; Jim Roberts, MD 44 Identification of distinctive volatile organic compounds in exhaled breath of preeclamptic women Shira Baram 1 , Marwan Hakiem 2 , Morad Nakhleh 3 , Hossam Haick 3 , Raed Salim 1 1 Emek Medical Center, Ob/Gyn, Afula, Israel, 2 Nazareth Hospital EMMS, Department of Obstetrics and Gynecology, Nazareth, Israel, 3 Technion, Department of Chemical Engineering and Russell Berrie Nanothecnology Institute, Haifa, Israel OBJECTIVE: To explore the spectrum of volatile organic compounds in the exhaled breath among women with preeclampsia, and to test the feasibility of nanomaterials based sensors array to detect pre- eclampsia by breath samples analysis. STUDY DESIGN: Exhaled alveolar breath was prospectively collected from 3 groups of women aged 18-40 years: preeclamptic women, healthy pregnant women at a gestational age of 24 weeks or more and healthy non-pregnant women. The nature of the exhaled breath was tested by a gas chromatography linked to mass spectrometry technique. A diagnostic model was then developed based on the responses of a tailor made array of cross reactive nano-sensors based on organically functionalized gold nano-particles. RESULTS: Overall, 92 women were included: 31 preeclamptic women, 31 healthy pregnant women and 30 healthy non-pregnant women. Out of 25 volatile organic compounds identied in breath, two compounds, Octanal and 5-(2-methylprpyl) nonane were signi- cantly higher among the preeclamptic women compared to the healthy pregnant group (p<0.05), (gure 1). Both compounds are hydrocarbon and considered signs of excessive oxidative stress activity. Using six sensing features extracted from the sensor array, a discriminative factor analysis model was obtained and tested with K-fold cross validation method. The sensor array was able to identify the breath samples of the preeclampsia group compared with healthy pregnant women with a sensitivity of 80%, specicity of 88% and accuracy of 84% (gure 2). Additionally, the sensitivity, specicity and accuracy were 92%, 81% and 87% respectively when comparing preeclamptic women with healthy non-pregnant women. CONCLUSION: Preeclamptic women have distinctive exhaled volatiles spectrum that could be accurately detected by an array of nano- material-based sensors. 45 Effect of high fat diet on metabolic programming in offspring born to hypertensive mother Monica Longo 1 , Jerrie Refuerzo 1 , Lovepreet Mann 1 , Mateo Leon 1 , Hind Moussa 1 , Baha Sibai 1 , Sean Blackwell 1 1 UT Health- University of Texas Medical School at Houston, OB/GYN, Houston, TX OBJECTIVE: We previously reported that mice born to hypertensive mother, lacking endothelial nitric oxide synthase (NOS3), are hy- pertensive. We hypothesized that offspring born to hypertensive mother, and placed on high fat diet (HFD) will undergo altered developmental programming, making them at increased risk of developing metabolic syndrome. STUDY DESIGN: Homozygous NOS3 knockout (KO) and wild type (WT) mice were cross-bred to produce heterozygous offspring: S32 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015 Oral Concurrent Session 4 ajog.org

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Page 1: 45: Effect of high fat diet on metabolic programming in offspring born to hypertensive mother

Oral Concurrent Session 4 ajog.org

Friday, February 6, 2015 d 1:15 pm e 3:30 pm d Indigo BF

HYPERTENSION

Abstracts 44 e 52Moderators: Virginia Winn, MD; Jim Roberts, MD

44

Identification of distinctive volatile organic compoundsin exhaled breath of preeclamptic womenShira Baram1, Marwan Hakiem2, Morad Nakhleh3,Hossam Haick3, Raed Salim1

1Emek Medical Center, Ob/Gyn, Afula, Israel, 2Nazareth Hospital EMMS,Department of Obstetrics and Gynecology, Nazareth, Israel, 3Technion,Department of Chemical Engineering and Russell Berrie NanothecnologyInstitute, Haifa, IsraelOBJECTIVE: To explore the spectrum of volatile organic compoundsin the exhaled breath among women with preeclampsia, and to testthe feasibility of nanomaterials based sensors array to detect pre-eclampsia by breath samples analysis.STUDY DESIGN: Exhaled alveolar breath was prospectively collectedfrom 3 groups of women aged 18-40 years: preeclamptic women,healthy pregnant women at a gestational age of 24 weeks or moreand healthy non-pregnant women. The nature of the exhaled breathwas tested by a gas chromatography linked to mass spectrometrytechnique. A diagnostic model was then developed based on theresponses of a tailor made array of cross reactive nano-sensors basedon organically functionalized gold nano-particles.RESULTS: Overall, 92 women were included: 31 preeclamptic women,31 healthy pregnant women and 30 healthy non-pregnant women.Out of 25 volatile organic compounds identified in breath, twocompounds, Octanal and 5-(2-methylprpyl) nonane were signifi-cantly higher among the preeclamptic women compared to thehealthy pregnant group (p<0.05), (figure 1). Both compoundsare hydrocarbon and considered signs of excessive oxidative stressactivity. Using six sensing features extracted from the sensor array,a discriminative factor analysis model was obtained and testedwith K-fold cross validation method. The sensor array was able toidentify the breath samples of the preeclampsia group comparedwith healthy pregnant women with a sensitivity of 80%, specificityof 88% and accuracy of 84% (figure 2). Additionally, the sensitivity,specificity and accuracy were 92%, 81% and 87% respectivelywhen comparing preeclamptic women with healthy non-pregnantwomen.CONCLUSION: Preeclamptic women have distinctive exhaled volatilesspectrum that could be accurately detected by an array of nano-material-based sensors.

S32 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2

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Effect of high fat diet on metabolic programming inoffspring born to hypertensive motherMonica Longo1, Jerrie Refuerzo1, Lovepreet Mann1, Mateo Leon1,Hind Moussa1, Baha Sibai1, Sean Blackwell11UT Health- University of Texas Medical School at Houston, OB/GYN,Houston, TXOBJECTIVE: We previously reported that mice born to hypertensivemother, lacking endothelial nitric oxide synthase (NOS3), are hy-pertensive. We hypothesized that offspring born to hypertensivemother, and placed on high fat diet (HFD) will undergo altereddevelopmental programming, making them at increased risk ofdeveloping metabolic syndrome.STUDY DESIGN: Homozygous NOS3 knockout (KO) and wild type(WT) mice were cross-bred to produce heterozygous offspring:

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Page 2: 45: Effect of high fat diet on metabolic programming in offspring born to hypertensive mother

ajog.org Hypertension Oral Concurrent Session 4

paternal-derived heterozygous (KOP) born to WT mother andmaternal-derived heterozygous (KOM) born to KO mothers, lackingNOS3. Maternal-KOM and Paternal-KOP offspring were placed onHFD or control diet (CD) at weaning for 4 wks and then dividedinto 4 groups: KOM-HFD, KOM-CD, KOP-HFD and KOP-CD.Offspring weight, oral glucose (OGTT) and insulin (ITT) tolerancetest were measured at 4 wks and after introduction of HFD (8-9wks). Blood pressure (BP), fasting insulin, cholesterol/triglycerideslevels were measured at 8-9 wks. 1-way-ANOVA and t-test were usedfor statistical analysis.RESULTS: Offspring weight was not different between groups.OGTT was significantly increased in KOM-HFD offspringcompared with KOM-CD, KOP-CD and KOP-HFD. (Fig.1) Afterinsulin bolus, glucose levels at 15 min were elevated in KOM-HFD vsKOM-CD, KOP-HFD (122.0�11.8; 49.4�5.6; 85.9�9.6 mg/mlrespectively, P<0.001). Fasting insulin levels were lower in KOM-HFD (0.25�0.06 ng/ml) vs KOP-HFD (0.77�0.17ng/ml). (Fig.2)BP was elevated in KOM-CD vs KOP-CD (157.6�6.3 vs132.2�4.5 mmHg, P<0.01) and this difference was maintained af-ter 4 wks on HFD. No differences were seen in cholesterol and tri-glyceride levels.CONCLUSION: Offspring born to hypertensive mother and fed HFDhave increased susceptibility for metabolic abnormalities comparedto their genetically identical counterpart. Maternal HTN is a riskfactor for abnormal fetal metabolic programming. This mousemodel maybe suited to evaluate metabolic syndrome, and to designinterventions to prevent long term cardiovascular disease.

Figure 1 Glucose tolerance test in KOM-CD andKOP-CD (control diet) and KOM-HFD and KOP-HFD(high fat diet)

Supplem

Figure 2 Fasting insulin level in offspring, maternal-KOM-HFD and paternal KOP-HFD

(HFD - high fat diet)

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Insulin growth factor 1 gene therapy restores alteredumbilical artery (UA) doppler indices in a mouse model ofgrowth restriction (IUGR)Khaled Omar1, Vicky Moore2, Chrissy Schulte2, Jeanne James2,Tarek Alsaied2, Rana Jawish1, Louis Muglia3, Mounira Habli11Cincinnati Childrens Hospital Research Center, Center for Fetal, Cellular &Molecular therapy, Cincinnati, OH, 2Cincinnati Childrens Hospital ResearchCenter, Cardiovascular Imaging Core Research Laboratory, Cincinnati, OH,3Cincinnati Childrens Hospital Research Center, Pediatrics, Cincinnati, OHOBJECTIVE: Previous work in our laboratory demonstrated that intra-placental gene therapy with adenoviral insulin growth factor1(AdIGF1) corrects fetal weight in a surgical mouse model of in-trauterine growth restriction. Doppler indices have not been evalu-ated. Aim of this study is to investigate the effect of intraplacentalIGF-1 over-expression on fetal/placental hemodynamics by assessingpre & post treatment UA Doppler indices in a surgical mouse modelof IUGRSTUDY DESIGN: Laparotomy was performed on pregnant C57mice(n¼24) at embryonic day 18 and pups were divided into 3groups. Control: Sham operated; IUGR: ligation of a uterine arterybranch; IUGR+IGF1: injection of Ad IGF1 after ligation. Pups weredelivered by C-section at day 20. 2D and trans-uterine Doppler im-aging was performed pre-ligation and prior to delivery. Data collectedwas: birth survival, UA peak systolic velocity(PSV), end diastolicvelocity(EDV), Systolic/Diastolic(S/D) ratio, pulsatility index(PI)and resistance index(RI) and heart rate (HR). Data analysed usingANOVARESULTS: Fetal survival in the IUGR group was 75%(18/24) vs.96%(23/24) in the IUGR+IGF1 vs 100% in the Control. IUGRgroup demonstrated AEDV in 12%(3/24) and REDV 12%(3/24) ofthe cases vs. only one case of REDV (1/24) in IUGR+IGF1. Ascompared to Sham, IUGR demonstrated a significant reductionin EDV, PSV, HR with a significant increase PI, RI and S/D ratio(Table1). Interestingly, IGF-Treated normalized altered indices inPSV(66�4.3vs 56�4.5,p¼0.02), EDV (6.2�0.3vs4.2�0.4,p¼0.007)and HR(78�10vs45�12p¼ 0.0001) as compared to IUGR group.IGF-Treated restored S/D ratio as compared to IUGR. No differenceswere detected in other variablesCONCLUSION: Intra-placental gene transfer of Ad-IGF1 restoresaltered umbilical artery Doppler indices in a surgical mouse modelof growth restriction. Compensatory changes in UA Doppler indices

ent to JANUARY 2015 American Journal of Obstetrics & Gynecology S33