- Email: [email protected]
48: Shotgun proteomics of the urine misfoldome identifies molecular signatures of preeclampsia subphenotypes
Oral Concurrent Session 4
Hypertension
after gene therapy open a new paradigm for assessing effective treatment and prevention in animal model of IUGR.
47 Like mother like daughter- low birthweight and preeclampsia tend to re-ocurre at the next generation
Yehonatan Sherf1, Eyal Sheiner1, Ilana Shoham Vardi1, Natalya Bilenko1 1
Ben-Gurion university of the Negev, Public Health, Beer-Sheva, Israel
OBJECTIVE: To evaluate the influence of intergenerational factors on
low birthweight (LBW) and preeclampsia. STUDY DESIGN: A retrospective population-based study was conducted. Perinatal information of 2314 triads of mothers, daughters giving births in a tertiary medical center between the years 19912012 and grandchildren was matched into the same database. Multivariate logistic regression analysis and generalized estimating equation cluster analysis was used to study the association between LBW and preeclampsia in both generations while controlling for confounders, and for clusters of families in the database. RESULTS: A total of 1493 mothers to, 1619 daughters, and 2314 grandchildren were included. LBW in mothers was found as a significant predictor for LBW in offspring (OR¼1.7, 95% CI 1.1-2.6, P¼0.012; Table) adjusted for maternal age, placental pathology, preeclampsia, parity. Likewise, preeclampsia was also noted as a significant intergenerational factor, adjusted for maternal age, and parity, in another model (adjusted OR¼ 2.9, 95% CI 1.5-5.7, P¼0.002; Table). CONCLUSION: Maternal low birthweight and preeclampsia are both independent risk factors for recurrence at the next generation.
ajog.org
pathogenesis of preeclampsia (PE). Different molecular entities of the misfoldome may reflect mechanisms that manifest as hypertension, but cannot be differentiated based on clinical criteria alone. We aimed to use ultraperformance proteomics to catalog and characterize the components of the PE urinary misfoldome and provide a molecular signature for various clinical phenotypes. STUDY DESIGN: Urine from 75 pregnant women were classified by strict clinical criteria in 6 groups: pregnant controls (CRL, n¼8), mild PE (mPE, n¼13), severe PE (sPE, n¼12), superimposed PE (spPE, n¼14), atypical preeclampsia (HELLPIUGR, n¼15), and non-PE proteinuria (n¼13). Misfoldome proteins were enriched by Congo Red (CR) precipitation. Native urine and CR precipitates were subjected to UPLC/MS/MS. Identities (IDs) were validated by Sequest and Mascot software. Accepted IDs had probability >99% and 2 matched peptides. Linear Discriminant Analysis (LDA) followed by pathway analysis on LDA clusters was employed to generate molecular PE subphenotypes. RESULTS: The proteome of CR precipitate differed from native urine. 199 peptides identified in sPE CR precipitates were absent in native urine. The peptides of all CR precipitates matched to 583 unique IDs. LDA identified 3 discriminating axes producing near perfect separation between atypical PE and all other groups (Figure). CRLs and non-PE proteinuric women clustered together indicating molecular similarity; sPE and mPE clustered apart implying dissimilarity. The spPE clustered between sPE and mPE. The highest scoring pathway within the atypical PE molecular cluster was protein folding/maturation of the angiotensinogen pathway, outnumbering the IDs of bradykinin/kalidin system that had the highest representation in sPE. CONCLUSION: Proteomic analysis of the urine misfoldome provides insights into the molecular mechanism of various PE subphenotypes.
Models summary - intergenerational factors
*adjusted for maternal age, placental pathology preeclampsia, parity. **adjusted for maternal age, parity.
48 Shotgun proteomics of the urine misfoldome identifies molecular signatures of preeclampsia subphenotypes
Irina Buhimschi1, Hongwu Jing2, Michelle Axe3, William Ray4, Guomao Zhao1, Chengsi Huang2, Yang Song2, Vicki Wysocki2, Catalin Buhimschi5
1 Nationwide Children’s Hospital, Center for Perinatal Research, Columbus, OH, 2The Ohio State University, Department of Chemistry and Biochemistry, Columbus, OH, 3Otterbein University, Westerville, OH, 4Nationwide Children’s Hospital, Battelle Center for Mathematical Medicine, Columbus, OH, 5The Ohio State University College of Medicine, Department of Obstetrics and Gynecology, Columbus, OH
OBJECTIVE: The misfoldome sums all proteins with propensity to
aggregate into amyloid-like fibrils and has been implicated in the
49 Dichorionic twin ultrasound surveillance e four-weekly significantly underperforms two-weekly ultrasound: results of the prospective multicenter ESPRiT study
Siobhan Corcoran1, Fionnuala Breathnach1, Gerard Burke2, Fionnuala McAuliffe3, Michael Geary4, Sean Daly5, John Higgins6, Alyson Hunter7, John Morrison8, Rhona Mahony9, Patrick Dicker1, Elizabeth Tully1, Fergal Malone1 1 RCSI, Dublin, Ireland, 2University of Limerick, Limerick, Ireland, 3UCD, Dublin, Ireland, 4Rotunda Hospital, Dublin, Ireland, 5Coombe Women and Infants University Hospital, Dublin, Ireland, 6UCC, COrk, Ireland, 7Royal
S34 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
Hypertension
after gene therapy open a new paradigm for assessing effective treatment and prevention in animal model of IUGR.
47 Like mother like daughter- low birthweight and preeclampsia tend to re-ocurre at the next generation
Yehonatan Sherf1, Eyal Sheiner1, Ilana Shoham Vardi1, Natalya Bilenko1 1
Ben-Gurion university of the Negev, Public Health, Beer-Sheva, Israel
OBJECTIVE: To evaluate the influence of intergenerational factors on
low birthweight (LBW) and preeclampsia. STUDY DESIGN: A retrospective population-based study was conducted. Perinatal information of 2314 triads of mothers, daughters giving births in a tertiary medical center between the years 19912012 and grandchildren was matched into the same database. Multivariate logistic regression analysis and generalized estimating equation cluster analysis was used to study the association between LBW and preeclampsia in both generations while controlling for confounders, and for clusters of families in the database. RESULTS: A total of 1493 mothers to, 1619 daughters, and 2314 grandchildren were included. LBW in mothers was found as a significant predictor for LBW in offspring (OR¼1.7, 95% CI 1.1-2.6, P¼0.012; Table) adjusted for maternal age, placental pathology, preeclampsia, parity. Likewise, preeclampsia was also noted as a significant intergenerational factor, adjusted for maternal age, and parity, in another model (adjusted OR¼ 2.9, 95% CI 1.5-5.7, P¼0.002; Table). CONCLUSION: Maternal low birthweight and preeclampsia are both independent risk factors for recurrence at the next generation.
ajog.org
pathogenesis of preeclampsia (PE). Different molecular entities of the misfoldome may reflect mechanisms that manifest as hypertension, but cannot be differentiated based on clinical criteria alone. We aimed to use ultraperformance proteomics to catalog and characterize the components of the PE urinary misfoldome and provide a molecular signature for various clinical phenotypes. STUDY DESIGN: Urine from 75 pregnant women were classified by strict clinical criteria in 6 groups: pregnant controls (CRL, n¼8), mild PE (mPE, n¼13), severe PE (sPE, n¼12), superimposed PE (spPE, n¼14), atypical preeclampsia (HELLPIUGR, n¼15), and non-PE proteinuria (n¼13). Misfoldome proteins were enriched by Congo Red (CR) precipitation. Native urine and CR precipitates were subjected to UPLC/MS/MS. Identities (IDs) were validated by Sequest and Mascot software. Accepted IDs had probability >99% and 2 matched peptides. Linear Discriminant Analysis (LDA) followed by pathway analysis on LDA clusters was employed to generate molecular PE subphenotypes. RESULTS: The proteome of CR precipitate differed from native urine. 199 peptides identified in sPE CR precipitates were absent in native urine. The peptides of all CR precipitates matched to 583 unique IDs. LDA identified 3 discriminating axes producing near perfect separation between atypical PE and all other groups (Figure). CRLs and non-PE proteinuric women clustered together indicating molecular similarity; sPE and mPE clustered apart implying dissimilarity. The spPE clustered between sPE and mPE. The highest scoring pathway within the atypical PE molecular cluster was protein folding/maturation of the angiotensinogen pathway, outnumbering the IDs of bradykinin/kalidin system that had the highest representation in sPE. CONCLUSION: Proteomic analysis of the urine misfoldome provides insights into the molecular mechanism of various PE subphenotypes.
Models summary - intergenerational factors
*adjusted for maternal age, placental pathology preeclampsia, parity. **adjusted for maternal age, parity.
48 Shotgun proteomics of the urine misfoldome identifies molecular signatures of preeclampsia subphenotypes
Irina Buhimschi1, Hongwu Jing2, Michelle Axe3, William Ray4, Guomao Zhao1, Chengsi Huang2, Yang Song2, Vicki Wysocki2, Catalin Buhimschi5
1 Nationwide Children’s Hospital, Center for Perinatal Research, Columbus, OH, 2The Ohio State University, Department of Chemistry and Biochemistry, Columbus, OH, 3Otterbein University, Westerville, OH, 4Nationwide Children’s Hospital, Battelle Center for Mathematical Medicine, Columbus, OH, 5The Ohio State University College of Medicine, Department of Obstetrics and Gynecology, Columbus, OH
OBJECTIVE: The misfoldome sums all proteins with propensity to
aggregate into amyloid-like fibrils and has been implicated in the
49 Dichorionic twin ultrasound surveillance e four-weekly significantly underperforms two-weekly ultrasound: results of the prospective multicenter ESPRiT study
Siobhan Corcoran1, Fionnuala Breathnach1, Gerard Burke2, Fionnuala McAuliffe3, Michael Geary4, Sean Daly5, John Higgins6, Alyson Hunter7, John Morrison8, Rhona Mahony9, Patrick Dicker1, Elizabeth Tully1, Fergal Malone1 1 RCSI, Dublin, Ireland, 2University of Limerick, Limerick, Ireland, 3UCD, Dublin, Ireland, 4Rotunda Hospital, Dublin, Ireland, 5Coombe Women and Infants University Hospital, Dublin, Ireland, 6UCC, COrk, Ireland, 7Royal
S34 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015