Objectives: Here, we performed a pathophysiological examination of the vascular function of rodent in the presence of placental protein 13 (PP13) and its implication to regulate the development of preeclampsia. Methods: Single i.v. injection and prolonged in vivo exposure to PP13 via osmotic pumps were performed in gravid and non-gravid rats to examine the influence of PP13 on blood pressure and heart rate in animals. The effect of PP13 was also examined in isolated uterine and mesenteric arteries, along with the examination of placental blood supply. Results: Human PP13 has a major impact on the maternal cardiovascular system of rodents by reducing blood pressure, either at single or prolonged exposure, and causing significant vasodilatation in isolated arteries. Prolonged exposure was followed by increased elaboration and angiogenesis of the uteroplacental arteries supplying the placenta. Conclusion: This is the first study describing effects of PP13 on vasodilatation and uterine artery remodeling. The results imply that PP13 may have a physiological role in improving uteroplacental blood flow. The findings of this study make it tempting to speculate that keeping PP13 levels within a certain ‘therapeutic window' during pregnancy may facilitate proper adaptation of the maternal vasculature to pregnancy.

1.
ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, 2002. American College of Obstetricians and Gynecologists. ACOG Committee on Obstetric Practice. Int J Gynaecol Obstet 2002;77:67-75.
2.
World Health Organization: Make Every Mother and Child Count. World Health Report, 2005. Geneva, World Health Organization, 2005.
3.
Huppertz B: Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 2008;51:970-975.
4.
Cetin I, Huppertz B, Burton G, Cuckle H, Gonen R, Lapaire O, Mandia L, Nicolaides K, Redman C, Soothill P, Spencer K, Thilaganathan B, Williams D, Meiri H: 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 1):S4-S16.
5.
Goswami D, Tannetta DS, Magee LA, Fuchisawa A, Redman CW, Sargent IL, von Dadelszen P: Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta 2006;27:56-61.
6.
Gupta AK, Rusterholz C, Huppertz B, Malek A, Schneider H, Holzgreve W, Hahn S: A comparative study of the effect of three different syncytiotrophoblast microparticles preparations on endothelial cells. Placenta 2005;26:59-66.
7.
Redman CW, Sargent IL: Latest advances in understanding preeclampsia. Science 2005;308:1592-1594.
8.
Redman CW, Sargent IL: Circulating microparticles in normal pregnancy and pre-eclampsia. Placenta 2008;29(suppl A):S73-S77.
9.
Pijnenborg R, Vercruysse L, Hanssens M: Fetal-maternal conflict, trophoblast invasion, preeclampsia, and the red queen. Hypertension 2008;27:183-196.
10.
McNamara JM, Kay HH: Placental hormones: Physiology, disease, and prenatal diagnosis; in Kay HH, Nelson DM, Wang Y (eds): The Placenta. From Development to Disease. Oxford, Wiley-Blackwell, 2011, chapter 8, p 57.
11.
Burger O, Pick E, Zwickel J, Klayman M, Meiri H, Slotky R, Mandel S, Rabinovitch L, Paltieli Y, Admon A, Gonen R: Placental protein 13 (PP-13): effects on cultured trophoblasts, and its detection in human body fluids in normal and pathological pregnancies. Placenta 2004;25:608-622.
12.
Than NG, Pick E, Bellyei S, Szigeti A, Burger O, Berente Z, Janaky T, Boronkai A, Kliman H, Meiri H, Bohn H, Than GN, Sumegi B: Functional analyses of placental protein 13/galectin-13. Eur J Biochem 2004;271:1065-1078.
13.
Balogh A, Pozsgay J, Matkó J, Dong Z, Kim CJ, Várkonyi T, Sammar M, Rigó J, Meiri H, Romero R, Papp Z, Than NG: Placental protein 13 (PP13/Galectin-13) undergoes lipid raft-associated subcellular redistribution in the syncytiotrophoblast in preterm preeclampsia and HELLP syndrome. Am J Obstet Gynecol 2011;205:156.e1-e14.
14.
Gonen R, Shahar R, Grimpel YI, Chefetz I, Sammar M, Meiri H, Gibor Y: Placental protein 13 as an early marker for pre-eclampsia: a prospective longitudinal study. BJOG 2008;115:1465-1472.
15.
Chafetz I, Kuhnreich I, Sammar M, Tal Y, Gibor Y, Meiri H, Cuckle H, Wolf M: First-trimester placental protein 13 screening for preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol 2007;197:35.e1-e7.
16.
Romero R, Kusanovic JP, Than NG, Erez O, Gotsch F, Espinoza J, Edwin S, Chefetz I, Gomez R, Nien JK, Sammar M, et al: First-trimester maternal serum PP13 in the risk assessment for preeclampsia. Am J Obstet Gynecol 2008;199:122.e1-e11.
17.
Khalil A, Cowans NJ, Spencer K, Goichman S, Meiri H, Harrington K: First-trimester markers for the prediction of pre-eclampsia in women with a-priori high risk. Ultrasound Obstet Gynecol 2010;35:671-679.
18.
Worthelbrew EJ, Koster MP, Cuckle HS, Stoutenbeek PH, Schielen PC, Visser GH: First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia. BJOG 2010;117:1384-1389.
19.
Huppertz B, Sammar M, Chefetz I, Neumaier-Wagner P, Bartz C, Meiri H: Longitudinal determination of serum placental protein 13 during development of preeclampsia. Fetal Diagn Ther 2008;24:230-236.
20.
Farina A, Zucchini C, Sekizawa A, Purwosunu Y, de Sanctis P, Santarsiero G, Rizzo N, Morano D, Okai T: Performance of messenger RNAs circulating in maternal blood in the prediction of preeclampsia at 10-14 weeks. Am J Obstet Gynecol 2010;203:e1-e6.
21.
Sekizawa A, Purwosunu Y, Yoshimura S, Nakamura M, Shimizu H, Okai T, Rizzo N, Farina A: PP13 mRNA expression in trophoblasts from preeclamptic placentas. Reprod Sci 2009;16:408-413.
22.
Sammar M, Nisemblat S, Fleischfarb Z, Golan A, Sadan O, Meiri H, Huppertz B, Gonen R: Placenta-bound and body fluid PP13 and its mRNA in normal pregnancy compared to preeclampsia, HELLP and preterm delivery. Placenta 2011;32(suppl):S30-S36.
23.
Than NG, Romero R, Goodman M, Weckle A, Xing J, Dong Z, Xu Y, Tarquini F, Szilagyi A, Gal P, Hou Z, Tarca AL, et al: A primate subfamily of galectins expressed at the maternal-fetal interface that promote immune cell death. Proc Natl Acad Sci USA 2009;106:9731-9736.
24.
Kliman HJ, Sammar M, Grimpel Y-I, Lynch SK, Milano KM, Pick E, Bejar J, Arad A, Lee JJ, Meiri H, Gonen R: Placental protein 13 and decidual zones of necrosis: an immunologic diversion that may be linked to preeclampsia. Reproduct Sci, DOI: 10.1177/1933719111424445.
25.
Than NG, Romero R, Meiri H, Erez O, Xu Y, Targuini F, Barna L, Szilagvi A, Ackerman R, Sammar M, Fule T, et al: PP13, maternal ABO blood groups and the risk assessment of pregnancy complications. PLoS one 2011;6:e21564.
26.
Svavarsdottir AH, Gizurarson S, Franzson L, Smarason AK: Functional behavior of placental protein 13 (PP13) and its involvement in preeclampsia, thesis; University of Iceland, 2008.
27.
Mohamood I: Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development. Adv Drug Delivery Rev 2007;59:1177-1192.
28.
Mandalà M, Gokina N, Barron C, Osol G: Endothelial-derived hyperpolarization factor (EDHF) contributes to PIGF-Induced dilation of mesenteric resistance arteries from pregnant rats. J Vasc Res 2012;49:43-49.
29.
Colton I, Mandalà M, Morton J, Davidge ST, Osol G: Influence of constriction, wall tenstion, smooth muscle activation and cellular deformation on rat resistance artery vasodilator reactivity. Cell Physiol Biochem 2012;29:883-892.
30.
Visegrády B, Than NG, Kilár F, Sümegi B, Than GN, Bohn H: Homology modeling and molecular dynamics studies of human placental tissue protein 13 (galectin-13). Protein Eng 2001;14:875-880.
31.
Björklund N, Dantzer V, Leiser R: Comparative placentation in laboratory animals. Scand J Lab Anim Sci 1989;16:129-158.
32.
Than NG, Abdul Rahman O, Magenheim R, Nagy B, Fule T, Hargitai B, Sammar M, Hupuczi P, Tarca AL, Szabo G, Kovalszky I, Meiri H, Sziller I, Rigo J Jr, Romero R, Papp Z: Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome. Virchows Arch 2008;453:387-400.
33.
Gebhardt S, Bruiners N, Hillerman R: A novel exonic variant (221delT) in the LGALS13 gene encoding placental protein 13 (PP13) is associated with preterm labour in a low risk population. J Reprod Immunol 2009:82:166-173.
34.
Soreq H, Wolf Y: NeurimmiRs: microRNAs in the neuroimmune interface. Trends Mol Med 2011;17:548-555.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.