458: maternal long-term cardiovascular function in an animal model of preeclampsia

458 MATERNAL LONG-TERM CARDIOVASCULAR FUNCTION IN AN ANIMAL MODEL OFPREECLAMPSIA EGLE BYTAUTIENE1, FANGXIAN LU1, ESTHER TAMAYO1, ANCIZARBETANCOURT1, GARY D.V. HANKINS1, GARLAND D. ANDERSON1, MONICA LONGO1,GEORGE R. SAADE1, 1The University of Texas Medical Branch, Obstetrics and Gyne-cology, Galveston, Texas

OBJECTIVE: Epidemiological studies suggest that preeclampsia is associatedwith an increased risk of cardiovascular diseases (CVD) in the mothers later in life.Our aim was to evaluate the long-term effects of preeclampsia on vascular functionin well characterized mouse model of preeclampsia induced by sFlt-1 over-expres-sion.

STUDY DESIGN: CD-1 mice at day 8 of gestation were injected via the tail veinwith adenovirus carrying Flt1 (AdsFlt1, 109 PFU/100 muL), or the murineIgG2alphaFc fragment as virus control (AdmFc, 109 PFU/100 muL), or saline (100muL). The mothers were investigated 6-8 months after delivery. Blood pressure(BP) was recorded in the conscious unrestrained animals by telemetry thru a cath-eter inserted into the aortic arch. The mice were then sacrificed, their carotid arter-ies were mounted in a wire myograph for isometric tension recording. The vascularrelaxant properties were evaluated using acetylcholine, sodium nitroprusside, andisoproterenol. The contractile vascular properties were investigated using phe-nilephrine, thromboxane A2 mimetic, and serotonin.

RESULTS: sFlt-1 levels at 6-8 months postpartum had returned to normal levelsand was comparable between the 3 groups. There was no statistically significantdifference in BP between the postpartum mice treated during pregnancy with Ads-Flt1, AdmFc, or saline. No differences between the groups were observed in thevascular reactivity as well.

CONCLUSION: The previously characterized effects of over-ex[ression of sFlt-1on blood pressure and altered vascular function is limited to pregnancy and doesnot appear to have long-term effect on the mothers postpartum. These data favorthe hypothesis that preeclampsia per se is not a risk factor for maternal CVD. Theepidemiological findings of increased CVD in women with history of preeclampsiaare likely the result of preexisting risk factors common to preeclampsia and CVD.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2007.10.477

459 MICRO RNA: A CENTRAL NEW PLAYER IN POST-TRANSCRIPTIONAL REGULATIONPATHWAY IN PREECLAMPSIA YARIV YOGEV1, NIR MELAMED1, RONY CHEN1, JACOBBAR1, AYELET CHAJUT2, NOGA YERUSHALMI2, HILA BENJAMIN2, MOSHE HOD1, 1HelenSchneider Hospital for Women, Rabin Medical Center, Petah Tiqwa, and SacklerFaculty of Medicine, Tel Aviv University, Obstetrics and Gynecology, Tel Aviv,Israel, 2Rosetta Genomics Ltd, Rehovot, Israel

OBJECTIVE: MicroRNAs (miRNA) are short sequences (20-22 nt) non-codingRNAs that regulate gene expression through post-transcriptional suppression ofmRNA. They have been preserved throughout evolution reflecting their impor-tance in gene regulation, and shown to play a central role in biological processessuch as development and in human diseases. It was suggested that in preeclampsia(PET) specific miRNA are expressed in the placenta. However, only limited num-bers of miRNA were evaluated (approx. 160) and the presence of miRNA in bodyfluids was not assessed. We aimed to determine which miRNA are expressed inuterine myometrium, placenta, amniotic fluid and maternal serum in severe PET.

STUDY DESIGN: In a prospective study, specimen of uterine myometrium andplacenta were assessed at delivery for the presence of approximately 700 differentmiRNA in 38 women, of them; 11 with severe PET and 27 without. All womenunderwent cesarean section prior to spontaneous onset of delivery. miRNAs wereextracted from the fresh tissue and their expression level was measured using ahighly sensitive microarray tool developed by Rosetta Genomics. Body fluids suchas maternal serum and amniotic fluid were also used for miRNA extraction, and theidentified differentially expressed miRNA in the placenta, were tested in those sam-ples using an ultra sensitive and specific quantitative Realtime PCR.

RESULTS: 1. Significant differential expression of unique miRNA was found inthe placenta and amniotic fluid of women with and without PET. 2. Some of thedifferentially expressed miRNAs were found to be differentially expressed also inthe serum samples of the same women. 3. No difference was found in miRNAexpression from myometrium samples between both groups.

CONCLUSION: Specific changes in the expression pattern of miRNA are presentin both placenta and serum of women with severe PET. These findings may suggestthat miRNAs play an essential role in the pathogenesis of PET.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2007.10.478

460 NULLIPAROUS WOMEN WHO UNDERGO CVS ARE AT INCREASED RISK OFDEVELOPING PREECLAMPSIA WILLIAM GROBMAN1, MELISSA AUGER1, LEESHULMAN1, SHERMAN ELIAS1, 1Northwestern University, Chicago, Illinois

OBJECTIVE: To evaluate the association between invasive prenatal diagnosisand the subsequent development of preeclampsia.

STUDY DESIGN: Using a cohort design, we compared women who had and whohad not undergone an invasive prenatal diagnostic procedure (i.e. second trimesteramniocentesis or first trimester chorionic villus sampling (CVS)) between Septem-ber 2002 and December 2003 at a single institution. Cases were matched withcontrols by maternal age on a 1:1 basis. Charts were abstracted for demographic,prenatal diagnostic and delivery data. Preeclampsia was defined as systolic bloodpressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mmHg on two occasions at least six hours apart in conjunction with proteinuria of atleast 2� on urinary dipstick or greater than 300 mg in a 24-hour urine collection.

RESULTS: Of the 653 women who underwent invasive prenatal diagnosis, 501(77%) had an amniocentesis and 152 (23%) had a CVS. Twenty-five women (1.9%)were diagnosed with preeclampsia, the frequency of which, in stratified analysis,was related to both parity and type of prenatal diagnostic procedure. Nulliparous(N) women undergoing CVS had a significantly (P � .001) higher frequency ofpreeclampsia (8.5%) than multiparous (M) women who had CVS (0.0%) as well asthose undergoing amniocentesis (N �3.8%; M � 1.4%) and those who did nothave a procedure (N � 1.9%; M � 0.8%). After stepwise regression, the onlyvariables associated with preeclampsia were nulliparity (OR 2.1, 95% CI 1.01-7.0),nulliparity and CVS (OR 4.2, 95% CI 1.4-12.6), and age less than 25 (OR 7.4, 95%CI 2.3-23.6).

CONCLUSION: Nulliparous woman who undergo CVS have an increased risk ofdeveloping preeclampsia. Further investigation should be directed to confirmingthis association.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2007.10.479

461 PROTEOMIC PROFILING OF URINE IN PREECLAMPSIA (PE) IDENTIFIES BIOMARKERSETS WHICH PREDICT OUTCOME AND DIFFERENTIATE THIS CONDITION FROM OTHERHYPERTENSIVE DISORDERS DURING GESTATION IRINA A. BUHIMSCHI1, GUOMAOZHAO1, EDMUND F. FUNAI1, IRA BERNSTEIN2, GEORGE R. SAADE3, CATALIN S.BUHIMSCHI1, 1Yale University, Ob./Gyn.&Reprod.Sci, New Haven, Connecticut,2University of Vermont, Ob./Gyn., Div. Mat. Fet. Med., Burlington, Vermont,3UTMB, Galveston, Ob./Gyn.&Reprod.Sci, Galveston, Texas

OBJECTIVE: Proteomic profiling of urine enabled discovery of novel biomarkersets characteristic of PE. We tested the clinical utility of a previously described urineproteomic profile to prospectively identify women with severe PE from other hy-pertensive proteinuric disorders during pregnancy.

STUDY DESIGN: 359 consecutive women were enrolled prospectively in thefollowing groups: i) normotensive controls (P-CRL, n�151); ii) mild PE (mPE,n�43); iii) chronic hypertension (crHTN, n�32); iv) severe PE (sPE, n�89); v)superimposed PE (spPE, n�34); vi) non-pregnant proteinuric controls (NP-CRL,n�10). In addition, 28 asymptomatic women at high risk for PE were followedlongitudinally across gestation. A proteomic fingerprint was generated by SELDI-TOF from fresh urine obtained on admission or prior to clinical manifestation.Scoring for 2 proteomic scores [UPSb (Boolean) & UPSr (Ranked)] was performedby an investigator unaware of clinical presentation or outcome. Results were vali-dated against urine sFlt-1-to-PlGF and protein-to-creatinine ratios.

RESULTS: Proteomic scores were significantly better predictors of sPE requir-ing delivery �34 weeks (Figure) than sFlt-1-to-PlGF (p�0.001) and protein-to-creatinine ratios (p�0.001). Women followed longitudinally who developed sPErequiring delivery (n�3) displayed positive proteomic scores �10 wks prior toclinical diagnosis. crHTN and P-CRL women exhibited the proteomic profile inonly 25% and 11% of cases, respectively. 88% of spPE women were correctly clas-sified. None of the proteinuric NP-CRL women displayed the PE proteomic pat-tern.

CONCLUSION: Our results provide evidence that urine proteomic profiling candiscriminate PE from other hypertensive disorders and predict outcome prior toclinical manifestation of the disease.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2007.10.480

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