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Choi, Hwang, Lee, Na, Ha, Lee, and Lee: Gene expression of heme oxygenase-1 and nitric oxide synthase on trophoblast of preeclampsia
Original Article
Korean Journal of Obstetrics & Gynecology

Korean Journal of Obstetrics & Gynecology 2011; 54(7): 341-348.

Published online: 18 July 2011

DOI: https://doi.org/10.5468/KJOG.2011.54.7.341

Gene expression of heme oxygenase-1 and nitric oxide synthase on trophoblast of preeclampsia

Song Kwon Choi, MD, Jong Yun Hwang, MD, Jiyeon Lee, MD, Sung Hun Na, MD, Joong Gyu Ha, MD, Hyang Ah Lee, MD, Dong Hun Lee, MD

Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea.

Corresponding author: Jong Yun Hwang, MD. Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, 17-1 Hyoja 3-dong, Chuncheon 200-722, Korea. Tel: +82-33-258-2307, Fax: +82-33-257-4636, rapidhwang@kangwon.ac.kr

Received 13 May 2011       Accepted 13 June 2011

Copyright © 2011. Korean Society of Obstetrics and Gynecology

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

The aim of this study was to evaluate the gene expression of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in placenta of preeclampsia.

Methods

Placenta were obtained from women with normal pregnancies (n=15) and severe preeclamptic (n=15) after informed consent and under the approval of IRB of Kangwon National University Hospital. The severe preeclampsia was diagnosed as high blood pressure and proteinuria. High blood pressure was defined as systolic blood pressure of >160 mm Hg or diastolic pressure of >110 mm Hg and proteinuria was defined as urine protein of >2 g/24 hr. We investigated mRNA expression of HO-1, iNOS and eNOS in both groups by real time polymerase chain reaction and immunohistochemistry. The Student's t-test was used for statistical analysis with SPSS ver. 12.0. P<0.05 was considered to be statistically significant.

Results

There were no significant differences in maternal age (P=1.181) and gestational age (P=0.30) between the two groups. Fetal birth weight from women with preeclampsia was significantly lower than that from normal pregnant women (P=0.002).
We detected differences in mRNA expression of placenta between both groups. Expression of HO-1 was decreased in placenta of preelamptic pregnancies compared to that from normal. However, expression of iNOS and eNOS was higher in preeclamptic group compared to normal.

Conclusion

We suggest that preeclampsia is associated with a decreased expression of HO-1 and increased expressions of iNOS and eNOS in placenta.

Keywords: Preeclampsia, Cytotrophoblast, Heme oxygenase-1

Figures and Tables

Fig. 1
Results of real time polymerase chain reaction. (A, B) The genes expression of iNOS and eNOS in placenta from women with preeclampsia groups were higher than these from normal groups. (C) The expression of HO-1 was decreased in placenta from women with preeclampsia compared to this from normal group. Data are mean ± SD. iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; HO-1, heme oxygenase-1. aP<0.01, bP<0.05.
kjog-54-341-g001
Fig. 2
Immunohistochemical staing for heme oxygenase-1 (HO-1) in placenta of women with preeclampsia. There is no signal of HO-1 in syncytiotrophoblast and cytotrophoblast, however some signal of that is in villous stromal cell (A) ×40, (B) ×200.
kjog-54-341-g002
Table 1
Primers sequence for real time polymerase chain reaction
kjog-54-341-i001

HO-1, heme oxygenase-1; iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase.

Table 2
Clinical characteristic in both groups
kjog-54-341-i002

Value are shown as mean±SD.

Student t-test.

References

1. Lain KY, Roberts JM. Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA. 2002. 287:3183–3186.
2. Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension. 2008. 51:970–975.
3. Redman CW, Sargent IL. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000. 21:597–602.
4. Wang Y, Gu Y, Zhang Y, Lewis DF. Evidence of endothelial dysfunction in preeclampsia: decreased endothelial nitric oxide synthase expression is associated with increased cell permeability in endothelial cells from preeclampsia. Am J Obstet Gynecol. 2004. 190:817–824.
5. Benedetto C, Marozio L, Neri I, Giarola M, Volpe A, Facchinetti F. Increased L-citrulline/L-arginine plasma ratio in severe preeclampsia. Obstet Gynecol. 2000. 96:395–399.
6. Wallace DH, Leveno KJ, Cunningham FG, Giesecke AH, Shearer VE, Sidawi JE. Randomized comparison of general and regional anesthesia for cesarean delivery in pregnancies complicated by severe preeclampsia. Obstet Gynecol. 1995. 86:193–199.
7. 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. 14:208–219.
8. Kim YM, Pae HO, Park JE, Lee YC, Woo JM, Kim NH, et al. Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2011. 14:137–167.
9. McCaig D, Lyall F. Inhibitors of heme oxygenase reduce invasion of human primary cytotrophoblast cells in vitro. Placenta. 2009. 30:536–538.
10. Zhao H, Wong RJ, Kalish FS, Nayak NR, Stevenson DK. Effect of heme oxygenase-1 deficiency on placental development. Placenta. 2009. 30:861–868.
11. Meekins JW, Pijnenborg R, Hanssens M, McFadyen IR, van Asshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol. 1994. 101:669–674.
12. Hayashi M, Hamada Y, Ohkura T. Elevation of granulocyte-macrophage colony-stimulating factor in the placenta and blood in preeclampsia. Am J Obstet Gynecol. 2004. 190:456–461.
13. Yoneyama Y, Suzuki S, Sawa R, Yoneyama K, Power GG, Araki T. Relation between adenosine and T-helper 1/T-helper 2 imbalance in women with preeclampsia. Obstet Gynecol. 2002. 99:641–646.
14. Bezerra PC, Leão MD, Queiroz JW, Melo EM, Pereira FV, Nóbrega MH, et al. Family history of hypertension as an important risk factor for the development of severe preeclampsia. Acta Obstet Gynecol Scand. 2010. 89:612–617.
15. Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR, Granger JP. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2008. 294:H541–H550.
16. Espinoza J, Romero R, Mee Kim Y, Kusanovic JP, Hassan S, Erez O, et al. Normal and abnormal transformation of the spiral arteries during pregnancy. J Perinat Med. 2006. 34:447–458.
17. Conrad KP, Vernier KA. Plasma level, urinary excretion, and metabolic production of cGMP during gestation in rats. Am J Physiol. 1989. 257:R847–R853.
18. Myatt L, Brewer AS, Langdon G, Brockman DE. Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation. Am J Obstet Gynecol. 1992. 166:224–230.
19. Lyall F. Development of the utero-placental circulation: the role of carbon monoxide and nitric oxide in trophoblast invasion and spiral artery transformation. Microsc Res Tech. 2003. 60:402–411.
20. Lyall F. Priming and remodelling of human placental bed spiral arteries during pregnancy--a review. Placenta. 2005. 26:Suppl A. S31–S36.
21. Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A. 1968. 61:748–755.
22. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997. 37:517–554.
23. Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J. 1988. 2:2557–2568.
24. Yoshiki N, Kubota T, Aso T. Expression and localization of heme oxygenase in human placental villi. Biochem Biophys Res Commun. 2000. 276:1136–1142.
25. Ihara N, Akagi R, Ejiri K, Kudo T, Furuyama K, Fujita H. Developmental changes of gene expression in heme metabolic enzymes in rat placenta. FEBS Lett. 1998. 439:163–167.
26. 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. 15:1158–1168.
27. Zenclussen AC, Lim E, Knoeller S, Knackstedt M, Hertwig K, Hagen E, et al. Heme oxygenases in pregnancy II: HO-2 is downregulated in human pathologic pregnancies. Am J Reprod Immunol. 2003. 50:66–76.
28. Lash GE, McLaughlin BE, MacDonald-Goodfellow SK, Smith GN, Brien JF, Marks GS, et al. Relationship between tissue damage and heme oxygenase expression in chorionic villi of term human placenta. Am J Physiol Heart Circ Physiol. 2003. 284:H160–H167.
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