Research Article
BibTex RIS Cite

INVESTIGATION OF SFLT-1 AND VEGF EXPRESSION IN NORMOTENSIVE AND PREECLAMPTIC PLACENTA. AN IMMUNOHISTOCHEMICAL STUDY

Year 2020, , 206 - 214, 25.12.2020
https://doi.org/10.33457/ijhsrp.766837

Abstract

Objectives: The pathogenesis of preeclampsia is still not clear, but endothelial dysfunction believed to be one of the most encountered problems during placenta development in preeclamptic patients. Both vascular endothelial growth factor (VEGF) and its antagonist, soluble Fms-Like tyrosine kinase-1 (sFlt-1), have roles in vascular function. In this study, we have investigated immunohistochemical expression of VEGF and sFlt-1 in term placenta of normotensive and preeclampsia patients.
Methods: Totally twenty term placentas were obtained from pregnant women of which 10 preeclampsia patient and 10 normotensive. Placentas were dissected and tissue samples were subjected to routine tissue processing protocol, then embedded in paraffin blocks. Serial sections were obtained from paraffin blocks and stained with H&E and PAS for routine histopathology. VEGF and sFlt-1 immunohistochemistry was performed to the sections.
Results: When compared to control group, severe pathological changes were observed in preeclamptic placentas. Increase in number of syncytial knots and intervillous bridges, hemorrhage in interstitium, dilatation and congestion in villous capillaries, increase in fibrin accumulation in villus stroma, and increase in thickening of basement membrane were very clear. VEGF expression was significantly higher in normotensive placentas compared to preeclamptic. On the other hand, sFlt-1 expression was significantly increased in preeclamptic placentas.
Conclusions: When the VEGF and sFlt-1 expression was considered, higher expression of sFlt-1 at preeclampsia, but decrease in VEGF expression, might be related to endothelial dysfunction in preeclampsia. Overall, this study demonstrates, imbalance between VEGF and sFlt-1 is one of the major reason of endothelial dysfunction in preeclamptic placenta.

Supporting Institution

Dicle University, Scientific Research Projects Coordination Unit

Project Number

Tıp.17.015

References

  • [1] J. Roberts and D. W. Cooper, "Pathogenesis and genetics of pre-eclampsia," The Lancet, vol. 357, no. 9249, pp. 53-56, 2001.
  • [2] U. Högberg, "The World Health Report 2005:``Make every mother and child count''—including Africans," ed: Sage Publications Sage UK: London, England, 2005.
  • [3] J. J. Walker, "Pre-eclampsia," The Lancet, vol. 356, no. 9237, pp. 1260-1265, 2000.
  • [4] W. P. Mutter and S. A. Karumanchi, "Molecular mechanisms of preeclampsia," Microvascular research, vol. 75, no. 1, pp. 1-8, 2008.
  • [5] J. Zhang et al., "Blood pressure dynamics during pregnancy and spontaneous preterm birth," American journal of obstetrics and gynecology, vol. 197, no. 2, pp. 162. e1-162. e6, 2007.
  • [6] E. Teran, A. Calle, and C. Escudero, "Endothelial dysfunction and preeclampsia," American journal of hypertension, vol. 20, no. 9, pp. 1026-1027, 2007.
  • [7] S. E. Maynard et al., "Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia," The Journal of clinical investigation, vol. 111, no. 5, pp. 649-658, 2003.
  • [8] A. C. Palei, F. T. Spradley, J. P. Warrington, E. M. George, and J. P. Granger, "Pathophysiology of hypertension in pre‐eclampsia: a lesson in integrative physiology," Acta physiologica, vol. 208, no. 3, pp. 224-233, 2013.
  • [9] J. P. Granger, B. T. Alexander, M. T. Llinas, W. A. Bennett, and R. A. Khalil, "Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction," Hypertension, vol. 38, no. 3, pp. 718-722, 2001.
  • [10] R. Dechend and F. C. Luft, "Angiogenesis factors and preeclampsia," Nature medicine, vol. 14, no. 11, pp. 1187-1188, 2008.
  • [11] N. A. Ibrahim and D. M. Khaled, "Histological and immunohistochemical study on human placental tissue in normal pregnancy and preeclampsia," Cell Biol, vol. 2, pp. 72-80, 2014.
  • [12] P. Navbir, N. Alka, and G. Antima, "Histological changes in placentae in pregnancies complicated by preeclampsia and eclampsia and correlation with fetal outcome," Int J Pharm Bio Sci, vol. 3, no. 2, pp. 551-60, 2012.
  • [13] R. R. Corrêa et al., "Placental morphometrical and histopathology changes in the different clinical presentations of hypertensive syndromes in pregnancy," Archives of Gynecology and Obstetrics, vol. 277, no. 3, pp. 201-206, 2008.
  • [14] I. de Luca Brunori et al., "Placental barrier breakage in preeclampsia: ultrastructural evidence," European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 118, no. 2, pp. 182-189, 2005.
  • [15] Z. Heidari, N. Sakhavar, H. Mahmoudzadeh-Sagheb, and T. Ezazi-Bojnourdi, "Stereological analysis of human placenta in cases of placenta previa in comparison with normally implanted controls," Journal of reproduction & infertility, vol. 16, no. 2, p. 90, 2015.
  • [16] B. K. Dwyer et al., "Variable expression of soluble fms-like tyrosine kinase 1 in patients at high risk for preeclampsia," The Journal of Maternal-Fetal & Neonatal Medicine, vol. 23, no. 7, pp. 705-711, 2010.
  • [17] A. Reuvekamp, F. V. Velsing‐Aarts, I. E. Poulina, J. J. Capello, and A. J. Duits, "Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre‐eclampsia," BJOG: An International Journal of Obstetrics & Gynaecology, vol. 106, no. 10, pp. 1019-1022, 1999.
  • [18] P. M. Bosio, T. Wheeler, F. Anthony, R. Conroy, C. O’Herlihy, and P. McKenna, "Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance," American journal of obstetrics and gynecology, vol. 184, no. 2, pp. 146-152, 2001.
  • [19] J. Cooper, A. Sharkey, J. McLaren, D. Charnock-Jones, and S. Smith, "Localization of vascular endothelial growth factor and its receptor, flt, in human placenta and decidua by immunohistochemistry," Reproduction, vol. 105, no. 2, pp. 205-213, 1995.
  • [20] X. Fan et al., "Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications," The Journal of clinical investigation, vol. 124, no. 11, pp. 4941-4952, 2014.
  • [21] R. J. Levine et al., "Soluble endoglin and other circulating antiangiogenic factors in preeclampsia," New England Journal of Medicine, vol. 355, no. 10, pp. 992-1005, 2006.
  • [22] B. C. Young, R. J. Levine, and S. A. Karumanchi, "Pathogenesis of preeclampsia," Annual Review of Pathology: Mechanisms of Disease, vol. 5, pp. 173-192, 2010.
Year 2020, , 206 - 214, 25.12.2020
https://doi.org/10.33457/ijhsrp.766837

Abstract

Project Number

Tıp.17.015

References

  • [1] J. Roberts and D. W. Cooper, "Pathogenesis and genetics of pre-eclampsia," The Lancet, vol. 357, no. 9249, pp. 53-56, 2001.
  • [2] U. Högberg, "The World Health Report 2005:``Make every mother and child count''—including Africans," ed: Sage Publications Sage UK: London, England, 2005.
  • [3] J. J. Walker, "Pre-eclampsia," The Lancet, vol. 356, no. 9237, pp. 1260-1265, 2000.
  • [4] W. P. Mutter and S. A. Karumanchi, "Molecular mechanisms of preeclampsia," Microvascular research, vol. 75, no. 1, pp. 1-8, 2008.
  • [5] J. Zhang et al., "Blood pressure dynamics during pregnancy and spontaneous preterm birth," American journal of obstetrics and gynecology, vol. 197, no. 2, pp. 162. e1-162. e6, 2007.
  • [6] E. Teran, A. Calle, and C. Escudero, "Endothelial dysfunction and preeclampsia," American journal of hypertension, vol. 20, no. 9, pp. 1026-1027, 2007.
  • [7] S. E. Maynard et al., "Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia," The Journal of clinical investigation, vol. 111, no. 5, pp. 649-658, 2003.
  • [8] A. C. Palei, F. T. Spradley, J. P. Warrington, E. M. George, and J. P. Granger, "Pathophysiology of hypertension in pre‐eclampsia: a lesson in integrative physiology," Acta physiologica, vol. 208, no. 3, pp. 224-233, 2013.
  • [9] J. P. Granger, B. T. Alexander, M. T. Llinas, W. A. Bennett, and R. A. Khalil, "Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction," Hypertension, vol. 38, no. 3, pp. 718-722, 2001.
  • [10] R. Dechend and F. C. Luft, "Angiogenesis factors and preeclampsia," Nature medicine, vol. 14, no. 11, pp. 1187-1188, 2008.
  • [11] N. A. Ibrahim and D. M. Khaled, "Histological and immunohistochemical study on human placental tissue in normal pregnancy and preeclampsia," Cell Biol, vol. 2, pp. 72-80, 2014.
  • [12] P. Navbir, N. Alka, and G. Antima, "Histological changes in placentae in pregnancies complicated by preeclampsia and eclampsia and correlation with fetal outcome," Int J Pharm Bio Sci, vol. 3, no. 2, pp. 551-60, 2012.
  • [13] R. R. Corrêa et al., "Placental morphometrical and histopathology changes in the different clinical presentations of hypertensive syndromes in pregnancy," Archives of Gynecology and Obstetrics, vol. 277, no. 3, pp. 201-206, 2008.
  • [14] I. de Luca Brunori et al., "Placental barrier breakage in preeclampsia: ultrastructural evidence," European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 118, no. 2, pp. 182-189, 2005.
  • [15] Z. Heidari, N. Sakhavar, H. Mahmoudzadeh-Sagheb, and T. Ezazi-Bojnourdi, "Stereological analysis of human placenta in cases of placenta previa in comparison with normally implanted controls," Journal of reproduction & infertility, vol. 16, no. 2, p. 90, 2015.
  • [16] B. K. Dwyer et al., "Variable expression of soluble fms-like tyrosine kinase 1 in patients at high risk for preeclampsia," The Journal of Maternal-Fetal & Neonatal Medicine, vol. 23, no. 7, pp. 705-711, 2010.
  • [17] A. Reuvekamp, F. V. Velsing‐Aarts, I. E. Poulina, J. J. Capello, and A. J. Duits, "Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre‐eclampsia," BJOG: An International Journal of Obstetrics & Gynaecology, vol. 106, no. 10, pp. 1019-1022, 1999.
  • [18] P. M. Bosio, T. Wheeler, F. Anthony, R. Conroy, C. O’Herlihy, and P. McKenna, "Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance," American journal of obstetrics and gynecology, vol. 184, no. 2, pp. 146-152, 2001.
  • [19] J. Cooper, A. Sharkey, J. McLaren, D. Charnock-Jones, and S. Smith, "Localization of vascular endothelial growth factor and its receptor, flt, in human placenta and decidua by immunohistochemistry," Reproduction, vol. 105, no. 2, pp. 205-213, 1995.
  • [20] X. Fan et al., "Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications," The Journal of clinical investigation, vol. 124, no. 11, pp. 4941-4952, 2014.
  • [21] R. J. Levine et al., "Soluble endoglin and other circulating antiangiogenic factors in preeclampsia," New England Journal of Medicine, vol. 355, no. 10, pp. 992-1005, 2006.
  • [22] B. C. Young, R. J. Levine, and S. A. Karumanchi, "Pathogenesis of preeclampsia," Annual Review of Pathology: Mechanisms of Disease, vol. 5, pp. 173-192, 2010.
There are 22 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Article
Authors

Firat Sahin 0000-0002-9343-4259

Murat Akkuş This is me 0000-0002-1659-1189

Uğur Şeker 0000-0002-1693-6378

Sevda Soker 0000-0001-6453-0033

Ebru Gokalp-ozkorkmaz 0000-0002-1967-4844

Elif Ağaçayak 0000-0002-4215-1371

Fırat Aşır 0000-0002-6384-9146

Project Number Tıp.17.015
Publication Date December 25, 2020
Submission Date July 9, 2020
Acceptance Date September 8, 2020
Published in Issue Year 2020

Cite

IEEE F. Sahin, M. Akkuş, U. Şeker, S. Soker, E. Gokalp-ozkorkmaz, E. Ağaçayak, and F. Aşır, “INVESTIGATION OF SFLT-1 AND VEGF EXPRESSION IN NORMOTENSIVE AND PREECLAMPTIC PLACENTA. AN IMMUNOHISTOCHEMICAL STUDY”, IJHSRP, vol. 5, no. 3, pp. 206–214, 2020, doi: 10.33457/ijhsrp.766837.

DOAJ_logo.png   scholar_logo_64dp.pngcrossref-logo-landscape-200.pnglogo.pnglogo-minik.png  CenterLogo.png researchgate-vector-logo.png SciLit logo ile ilgili görsel sonucuicon.png?w=170&fakeurl=1Medical Reads

https://upload.wikimedia.org/wikipedia/commons/2/20/DOAJ_logo.pnghttps://upload.wikimedia.org/wikipedia/commons/2/20/DOAJ_logo.pnghttps://upload.wikimedia.org/wikipedia/commons/2/20/DOAJ_logo.pnghttps://upload.wikimedia.org/wikipedia/commons/2/20/DOAJ_logo.png    Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial -NoDerivatives 4.0 International License.