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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
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1437-4331
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Volume 53, Issue 9

Issues

HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population

Silvia Galbiati
  • Corresponding author
  • Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Annalisa Inversetti / Vincenza Causarano
  • Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Stefania Stenirri
  • Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Nadia Soriani
  • Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Alessandro Ambrosi / Luca Valsecchi / Massimo Candiani / Laura Cremonesi
  • Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Maurizio Ferrari
  • Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • Università Vita-Salute San Raffaele, Milan, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Maddalena Smid
Published Online: 2014-12-02 | DOI: https://doi.org/10.1515/cclm-2014-0745

Abstract

Background: Pre-eclampsia (PE) is a hypertensive multisystem disorder, causing significant fetal-maternal mortality and morbidity worldwide. This study aims to define possible longitudinal predictive mRNA markers involved in the main pathogenic pathways of PE: inflammation [macrophage migration inhibitory factor (MIF)], hypoxia and oxidative stress [hypoxia inducible factor 1-α subunit (HIF1A) and β-site APP-cleaving enzyme-2 (BACE2)] and endothelial dysfunction [endoglin (ENG), fms-related tyrosine kinase-1 (FLT1) and vascular endothelial growth factor (VEGF)].

Methods: Peripheral blood was collected from 33 singleton pregnancies characterized by a high cardiovascular profile risk sampled consecutively at 6–16; 17–23; 24–30; 31–34; ≥35 weeks followed by the Obstetrics and Gynecology Unit of the San Raffaele Hospital in Milan. A real-time quantitative PCR reaction was performed on plasma RNA.

Results: Of the 33 women enrolled, nine developed PE. Until 23 weeks HIF1A was significantly higher in women who later developed PE compared to women who did not (p=0.049 and p=0.012 in the first and second blood collection). In the third time interval MIF (p=0.0005), FLT1 (p=0.024), ENG (p=0.0034) and BACE2 (p=0.044) appeared to be significantly increased while HIF1A was elevated even from 24 week onwards but not reaching the statistical significance. In the fourth time interval ENG mRNA still remained increased (p=0.037).

Conclusions: HIF1A, marker of hypoxia and oxidative stress, and MIF, marker of inflammation, seemed to be the most promising RNA markers, suggesting that hypoxia, principally, and inflammation may play an important role in PE pathogenesis.

Keywords: high risk population; hypoxia; inflammation; longitudinal study; pre-eclampsia; predictive mRNA markers

References

  • 1.

    Noris M, Perico N, Remuzzi G. Mechanisms of disease: pre-eclampsia. Nat Clin Pract Nephrol 2005;1:98–114.Google Scholar

  • 2.

    Cetin I, Huppertz B, Burton G, Cuckle H, Gonen R, Lapaire O, et al. Pregenesys pre-eclampsia markers consensus meeting: what do we require from markers, risk assessment and model systems to tailor preventive strategies? Placenta 2011;32(Suppl):S4–16.Web of ScienceCrossrefGoogle Scholar

  • 3.

    Sekizawa A, Purwosunu Y, Farina A, Shimizu H, Nakamura M, Wibowo N, et al. Prediction of pre-eclampsia by an analysis of placenta-derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation. Br J Obstet Gynaecol 2010;117:557–64.Google Scholar

  • 4.

    Purwosunu Y, Sekizawa A, Okazaki S, Farina A, Wibowo N, Nakamura N, et al. Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma. Am J Obstet Gynecol 2009;200:386.e1–7.Google Scholar

  • 5.

    Farina A, Zucchini C, Sekizawa A, Purwosunu Y, de Sanctis P, Santarsiero G, et al. Performance of messenger RNAs circulating in maternal blood in the prediction of pre-eclampsia at 10–14 weeks. Am J Obstet Gynecol 2010;203:575.e1–7.Web of ScienceGoogle Scholar

  • 6.

    Galbiati S, Causarano V, Pinzani P, Salvianti F, Orlando C, Smid M, et al. Evaluation of a panel of circulating DNA, RNA and protein potential markers of pregnancy pathologies. Clin Chem Lab Med 2010;48:791–4.Web of ScienceGoogle Scholar

  • 7.

    Vatten LJ, Eskild A, Nilsen TI, Jeansson S, Jenum PE, Staff AC. Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. Am J Obstet Gynecol 2007;196:239–e1.Web of ScienceGoogle Scholar

  • 8.

    Myatt L, Clifton R, Roberts J, Spong C, Wapner R, Thorp J Jr, et al. Can changes in angiogenic biomarkers between first and second trimesters of pregnancy predict development of pre-eclampsia in a low risk nulliparous patient population? Br J Obstet Gynaecol 2013;120:1183–91.Google Scholar

  • 9.

    Maynard SE, Crawford SL, Bathgate S, Yan J, Robidoux L, Moore M, et al. Gestational angiogenic biomarker patterns in high risk preeclampsia groups. Am J Obstet Gynecol 2013;209:53.e1–9.Google Scholar

  • 10.

    Kleinrouweler CE, Wiegerinck MM, Ris-Stalpers C, Bossuyt PM, van der Post JA, von Dadelszen P, et al. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis. Br J Obstet Gynaecol 2012;119:778–87.Google Scholar

  • 11.

    Laresgoiti-Servitje E. A leading role for the immune system in the pathophysiology of preeclampsia. J Leukoc Biol 2013;94:247–57.Web of ScienceGoogle Scholar

  • 12.

    Rovere-Querini P, Antonacci S, Dell’Antonio G, Angeli A, Almirante G, Cin ED, et al. Plasma and tissue expression of the long pentraxin 3 during normal pregnancy and preeclampsia. Obstet Gynecol 2006;108:148–55.Google Scholar

  • 13.

    Ashur-Fabian O, Yerushalmi GM, Mazaki-Tovi S, Steinberg DM, Goldshtein I, Yackobovitch-Gavan M, et al. Cell free expression of hif1α and p21 in maternal peripheral blood as a marker for preeclampsia and fetal growth restriction. PLoS One 2012;7:e37273.Google Scholar

  • 14.

    Galbiati S, Smid M, Gambini D, Ferrari A, Restagno G, Viora E, et al. Fetal DNA detection in maternal plasma throughout gestation. Hum Genet 2005;117:243–8.Google Scholar

  • 15.

    Schroeder BM. ACOG practice bulletin on diagnosing and managing preeclampsia and eclampsia. American College of Obstetricians and Gynecologists. Am Fam Physician 2002;66:330–1.Google Scholar

  • 16.

    Farina A. The role of RNAs and microRNAs in non-invasive prenatal diagnosis. J Clin Med 2014;3:440–52.Google Scholar

  • 17.

    Tal R. The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis. Biol Reprod 2012;87:134,1–8.Web of ScienceGoogle Scholar

  • 18.

    Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, et al. Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci USA 2006;103:18727–32.Google Scholar

  • 19.

    Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, et al. Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 2007;282:10873–80.Web of ScienceGoogle Scholar

  • 20.

    Sitras V, Paulssen RH, Grønaas H, Leirvik J, Hanssen TA, Vårtun A, et al. Differential placental gene expression in severe preeclampsia. Placenta 2009;30:424–33.Google Scholar

  • 21.

    Stockley JH, O’Neill C. The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimer’s disease brain. Biochem Soc Trans 2007;35:574–6.Web of ScienceGoogle Scholar

  • 22.

    Redman CW, Sargent IL, Staff AC. IFPA Senior Award Lecture: making sense of pre-eclampsia – two placental causes of pre-eclampsia? Placenta 2014;35(Suppl):S20–5.CrossrefPubMedGoogle Scholar

  • 23.

    Zamudio S, Borges M, Echalar L, Kovalenko O, Vargas E, Torricos T, et al. Maternal and fetoplacental hypoxia do not alter circulating angiogenic growth effectors during human pregnancy. Biol Reprod 2014;90:42.Web of ScienceGoogle Scholar

  • 24.

    van Rijn BB, Veerbeek JH, Scholtens LC, Post Uiterweer ED, Koster MP, Peeters LL, et al. C-reactive protein and fibrinogen levels as determinants of recurrent preeclampsia: a prospective cohort study. J Hypertens 2014;32:408–14.Web of ScienceGoogle Scholar

  • 25.

    Luedike P, Hendgen-Cotta UB, Sobierajski J, Totzeck M, Reeh M, Dewor M, et al. Cardioprotection through S-nitros(yl)ation of macrophage migration inhibitory factor. Circulation 2012;125:1880–9.Web of ScienceGoogle Scholar

  • 26.

    Rolfo A, Giuffrida D, Nuzzo AM, Pierobon D, Cardaropoli S, Piccoli E, et al. Pro inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia. PLoS One 2013;8:e59403.Web of ScienceCrossrefGoogle Scholar

  • 27.

    Purwosunu Y, Sekizawa A, Yoshimura S, Farina A, Wibowo N, Nakamura M, et al. Expression of angiogenesis-related genes in the cellular component of the blood of preeclamptic women. Reprod Sci 2009;16:857–64.Web of ScienceGoogle Scholar

  • 28.

    American College of Obstetricians and Gynecologists, issuing body. II.DNLM 1: Hypertension, pregnancy induced – practice guideline. WQ 244.Google Scholar

About the article

Corresponding author: Silvia Galbiati, Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy, Phone: +39 02 26434358, Fax: +39 02 26434351, E-mail:


Received: 2014-07-18

Accepted: 2014-10-30

Published Online: 2014-12-02

Published in Print: 2015-08-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 9, Pages 1339–1347, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-0745.

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