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Am J Perinatol 2014; 31(10): 883-890
DOI: 10.1055/s-0033-1363163
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of the Reduction of Spiral Artery Remodeling and Heme Oxygenase 1 in Mediating AT1-AA–Induced Hypertension and Intrauterine Growth Restriction in Pregnant Rats

Dan Zhang
1   Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China
,
Leilei Wang
1   Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China
,
Chong Qiao
1   Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China
,
Yang Yu
1   Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China
,
Lihua Fu
2   Department of Obstetrics and Gynaecology, Beijing Ditan Hospital Capital Medical University, Beijing, China
,
Tao Shang
1   Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China
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Publikationsverlauf

07. Februar 2012

24. Mai 2012

Publikationsdatum:
28. Mai 2014 (online)

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Abstract

Introduction: Recently, emerging evidence has indicated that preeclamptic women who have angiotensin receptor agonistic autoantibodies (AT1-AA), these antibodies contribute to features of the disease.

Aim: The purpose of this study was to determine the role of spiral artery remodeling in mediating AT1-AA–induced hypertension and intrauterine growth restriction in pregnant rats. We hypothesized that AT1-AA–mediated heme oxygenase 1 (HO-1) reduction contributes to decreased spiral artery remodeling. Rat AT1-AA and an HO-1 inducer were administered to pregnant rats.

Result: Mean arterial pressure (MAP) increased from 98 ± 4 mm Hg in normal pregnant rats to 113 ± 6 mm Hg in AT1-AA–infused rats (p < 0.05), which was significantly attenuated by the HO-1 inducer (103 ± 2 mm Hg). Fetal weight was also attenuated by HO-1 inducer, and kidney and liver development was adversely affected. Spiral artery remodeling was significantly reduced in AT1-AA-treated pregnant rats compared with that in normal pregnant rats, and this was significantly ameliorated by an HO-1 inducer.

Conclusion: Our findings demonstrate that AT1-AA-mediated HO-1 reduction contributes to reduced spiral artery remodeling, and is one mechanism whereby AT1-AA mediates hypertension and intrauterine growth retardation.

Keywords

antibodies - heme oxygenase 1 - intrauterine growth restriction - preeclampsia - spiral artery
 

  • References

  • 1 Lain KY, Roberts JM. Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA 2002; 287 (24) 3183-3186
    CrossrefPubMedSuche in Google Scholar
  • 2 Chesley LC. Hypertensive disorders in pregnancy. New York, NY: Appleton-Century-Crofts; 1978: 777-822
    Suche in Google Scholar
  • 3 Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet 2001; 357 (9249) 53-56
    CrossrefPubMedSuche in Google Scholar
  • 4 Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science 2005; 308 (5728) 1592-1594
    CrossrefPubMedSuche in Google Scholar
  • 5 Zhou CC, Zhang Y, Irani RA , et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 2008; 14 (8) 855-862
    CrossrefPubMedSuche in Google Scholar
  • 6 Walther T, Wallukat G, Jank A , et al. Angiotensin II type 1 receptor agonistic antibodies reflect fundamental alterations in the uteroplacental vasculature. Hypertension 2005; 46 (6) 1275-1279
    CrossrefPubMedSuche in Google Scholar
  • 7 Zhou CC, Ahmad S, Mi T , et al. Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling. Hypertension 2008; 51 (4) 1010-1019
    CrossrefPubMedSuche in Google Scholar
  • 8 Dechend R, Viedt C, Müller DN , et al. AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Circulation 2003; 107 (12) 1632-1639
    Suche in Google Scholar
  • 9 Yang X, Wang F, Chang H , et al. Autoantibody against AT1 receptor from preeclamptic patients induces vasoconstriction through angiotensin receptor activation. J Hypertens 2008; 26 (8) 1629-1635
    CrossrefPubMedSuche in Google Scholar
  • 10 Xia Y, Wen H, Bobst S, Day MC, Kellems RE. Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells. J Soc Gynecol Investig 2003; 10 (2) 82-93
    CrossrefPubMedSuche in Google Scholar
  • 11 Parrish MR, Wallace K, Tam Tam KB , et al. Hypertension in response to AT1-AA: role of reactive oxygen species in pregnancy-induced hypertension. Am J Hypertens 2011; 24 (7) 835-840
    CrossrefPubMedSuche in Google Scholar
  • 12 Le WD, Xie WJ, Appel SH. Protective role of heme oxygenase-1 in oxidative stress-induced neuronal injury. J Neurosci Res 1999; 56 (6) 652-658
    CrossrefPubMedSuche in Google Scholar
  • 13 Zhang M, Zhang BH, Chen L, An W. Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation. Cell Res 2002; 12 (2) 123-132
    CrossrefPubMedSuche in Google Scholar
  • 14 Zhao H, Wong RJ, Kalish FS, Nayak NR, Stevenson DK. Effect of heme oxygenase-1 deficiency on placental development. Placenta 2009; 30 (10) 861-868
    CrossrefPubMedSuche in Google Scholar
  • 15 Zhou CC, Irani RA, Zhang Y , et al. Angiotensin receptor agonistic autoantibody-mediated tumor necrosis factor-α induction contributes to increased soluble endoglin production in preeclampsia. Circulation 2010; 121 (3) 436-444
    CrossrefPubMedSuche in Google Scholar
  • 16 Fu ML, Leung PS, Wallukat G , et al. Agonist-like activity of antibodies to angiotensin II receptor subtype 1 (AT1) from rats immunized with AT1 receptor peptide. Blood Press 1999; 8 (5-6) 317-324
    CrossrefPubMedSuche in Google Scholar
  • 17 Wallukat G, Homuth V, Fischer T , et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999; 103 (7) 945-952
    CrossrefPubMedSuche in Google Scholar
  • 18 Wallukat G, Nissen E, Neichel D, Harris J. Spontaneously beating neonatal rat heart myocyte culture–a model to characterize angiotensin II AT1 receptor autoantibodies in patients with preeclampsia. In Vitro Cell Dev Biol–Anim 2002; 38: 376-377
    PubMedSuche in Google Scholar
  • 19 Geusens N, Verlohren S, Luyten C , et al. Endovascular trophoblast invasion, spiral artery remodelling and uteroplacental haemodynamics in a transgenic rat model of pre-eclampsia. Placenta 2008; 29 (7) 614-623
    CrossrefPubMedSuche in Google Scholar
  • 20 Vercruysse L, Caluwaerts S, Luyten C, Pijnenborg R. Interstitial trophoblast invasion in the decidua and mesometrial triangle during the last third of pregnancy in the rat. Placenta 2006; 27 (1) 22-33
    CrossrefPubMedSuche in Google Scholar
  • 21 Irani RA, Zhang Y, Blackwell SC , et al. The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia. J Exp Med 2009; 206 (12) 2809-2822
    CrossrefPubMedSuche in Google Scholar
  • 22 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-408
    CrossrefPubMedSuche in Google Scholar
  • 23 Matsumura G, Sasaki K. Megakaryocytes in the yolk sac, liver and bone marrow of the mouse: a cytometrical analysis by semithin light microscopy. J Anat 1989; 167: 181-187
    PubMedSuche in Google Scholar
  • 24 Siddiqui AH, Irani RA, Blackwell SC, Ramin SM, Kellems RE, Xia Y. Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity. Hypertension 2010; 55 (2) 386-393
    CrossrefPubMedSuche in Google Scholar
  • 25 Brosens JJ, Pijnenborg R, Brosens IA. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 2002; 187 (5) 1416-1423
    CrossrefPubMedSuche in Google Scholar
  • 26 Hung TH, Skepper JN, Charnock-Jones DS, Burton GJ. Hypoxia-reoxygenation: a potent inducer of apoptotic changes in the human placenta and possible etiological factor in preeclampsia. Circ Res 2002; 90 (12) 1274-1281
    CrossrefPubMedSuche in Google Scholar
  • 27 Dechend R, Gratze P, Wallukat G , et al. Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia. Hypertension 2005; 45 (4) 742-746
    CrossrefPubMedSuche in Google Scholar
  • 28 Hering L, Herse F, Geusens N , et al. Effects of circulating and local uteroplacental angiotensin II in rat pregnancy. Hypertension 2010; 56 (2) 311-318
    CrossrefPubMedSuche in Google Scholar
  • 29 Lyall F, Barber A, Myatt L, Bulmer JN, Robson SC. Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function. FASEB J 2000; 14 (1) 208-219
    PubMedSuche in Google Scholar
  • 30 Bainbridge SA, Farley AE, McLaughlin BE , et al. Carbon monoxide decreases perfusion pressure in isolated human placenta. Placenta 2002; 23 (8-9) 563-569
    CrossrefPubMedSuche in Google Scholar
  • 31 Ahmed A, Rahman M, Zhang X , et al. Induction of placental heme oxygenase-1 is protective against TNFalpha-induced cytotoxicity and promotes vessel relaxation. Mol Med 2000; 6 (5) 391-409
    PubMedSuche in Google Scholar
  • 32 Cudmore M, Ahmad S, Al-Ani B , et al. Negative regulation of soluble Flt-1 and soluble endoglin release by heme oxygenase-1. Circulation 2007; 115 (13) 1789-1797
    CrossrefPubMedSuche in Google Scholar
  • 33 Barber A, Robson SC, Myatt L, Bulmer JN, Lyall F. Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO-2 in preeclampsia and fetal growth restriction. FASEB J 2001; 15 (7) 1158-1168
    CrossrefPubMedSuche in Google Scholar
  • 34 Lyall F, Barber A, Myatt L, Bulmer JN, Robson SC. Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function. FASEB J 2000; 14 (1) 208-219
    PubMedSuche in Google Scholar