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Preeklamptik ve normotansif plasentalarda VEGF ve Vimentin ekspresyon düzeylerinin immunohistokimya ve Western Blot yöntemleri ile incelenmesi

Year 2016, Volume: 43 Issue: 3, 400 - 405, 01.09.2016

Abstract

Amaç: Bu çalışmada anjiogenezi stimule eden vasküler
endotel büyüme faktörü (VEGF) ve bir mezenşimal markır
olan vimentin proteinlerinin preeklamptik ve normotansif
plasentalardaki ekspresyon düzeylerini araştırmayı
amaçladık.
Yöntemler: Çalışmaya 35-38. haftalardaki doğum sonrası
plasentalar dahil edildi. 10 adet preeklamptik ve 10
adet normal plasenta kullanıldı. %10’ luk formaldehit solüsyonuna
atılan doku parçaları rutin parafin takiplerinden
sonra histopatolojik olarak incelendi. VEGF ve vimentin
protein düzeyleri Western Blot yöntemiyle ölçüldü.
Bulgular: Preeklamptik plasentalarda sinsisyal proliferasyonun
artmış olduğu izlendi. İntravillous sinsityal
düğümler, sinsityal ödem, kollajen artışı ve damarlarda
endotel hasar gözlendi. Preeklampsi (PE) sonucu plasentadaki
VEGF ve vimentin protein düzeylerinin artış
gösterdiği gözlendi.
Sonuç: Preeklamptik plasenta dokusunda fonksiyonel olmayan
VEGF ligandının reseptörüne bağlanamadığı için
VEGF miktarının arttığı ve bu durumun yetersiz anjiogeneze
neden olduğu olasıdır. Ayrıca preeklamptik plasentadaki
vimentin artışının vasküler permeabilitenin azalmasına
neden olabileceği düşünülmektedir.

References

  • 1. American College of Obstetricians and Gynecologists. Hypertension in Pregnancy. Obstet Gynecol 2013;122:1122–31.
  • 2. Steegers E, Von Dadelszen P, Duvekot J, Pijnenborg R. Pre-eclampsia. Lancet 2010;376:631–44.
  • 3. Saleh L, Verdonk K, Visser W, et al. The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia. Ther Adv Cardiovasc Dis 2016; DOI: 10.1177/1753944715624853.
  • 4. Sak S, Erdemoğlu M, Ağaçayak E, et al. Evaluation of serum Troponin I Levels in preeclampsia. Dicle Med J 2015;42:186–91
  • 5. Verdonk K, Visser W, Van Den Meiracker A, Danser A. The renin–angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad. Clin Sci (Lond) 2014;126:537–44.
  • 6. Maynard S, Epstein F, Karumanchi S. Pre-eclampsia and angiogenic imbalance. Annu Rev Med 2008;59:61–78.
  • 7. Walentin K, Hinze C, Schmidt-Ott KM. The basal chorionic trophoblast cell layer: An emerging coordinator of placenta development. Bioessays 2016;38:254–65.
  • 8. Davies JE, Pollheimer J, Yong HEJ, et al. Epithelial-mesenchymal transition during extravillous trophoblast differentiation. Cell Adh Migr 2016; DOI: 10.1080/19336918.
  • 9. Patel A and Dash PR. Formation of atypical podosomes in extravillous trophoblasts regulates extracellular matrix degradation. Eur J Cell Biol 2012;91:171–9.
  • 10. Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension 2013;62:1046–54.
  • 11. Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 2014;10:466–80.
  • 12. Zhou Y, Damsky CH, Fisher SJ. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? JClin Invest 1997;99:2152–64.
  • 13. Lee ES, Oh MJ, Jung JW, et al. The levels of circulating vascular endothelial growth factor and soluble Flt-1 in pregnancies complicated by preeclampsia. J Korean Med Sci 2007;22:94–8.
  • 14. Procopciuc LM, Caracostea G, Zaharie G, Stamatian F. Maternal/newborn VEGF-C936T interaction and its influence on the risk, severity and prognosis of preeclampsia, as well as on the maternal angiogenic profile. J Matern Fetal Neonatal Med 2014;27:1754–60.
  • 15. Kalay S, Cakcak B, Oztekin O, et al. The role of VEGF and its soluble receptor VEGFR-1 in preterm newborns of preeclamptic mothers with RDS. J Matern Fetal Neonatal Med 2013;26:978–83.
  • 16. Shirakawa T, Miyahara Y, Kenji Tanimura K, et al. Expression of Epithelial-Mesenchymal Transition-related Factors in Adherent Placenta. Int J Gynecol Pathol 2015;34:584–9.
  • 17. Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 2009;1796:75–90.
  • 18. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom BJOG 2011;118:1–203.
  • 19. Sezer SD, Küçük M, Döger FK, et al. VEGF, PIGF and HIF-1a in placentas of early- and late-onset pre-eclamptic patients. Gynecol Endocrinol 2013;29:797–800.
  • 20. Vuorela P, Hatva E, Lymboussaki A, et al. Expression of vascular endothelial growth factor and placenta growth factor in human placenta. Biol Reprod 1997;56:489–94.
  • 21. Anthony FW, Evans PW, Wheeler T, et al. Variation in detection of VEGF in maternal serum by immunoassay and the possible influence of binding proteins. Ann Clin Biochem 1997;34:276–80.
  • 22. Kupfermine MJ, Daniel Y, Englender T, et al. Vascular endothelial growth factor is increased in patients with preeclampsia. Am J Reprod Immunol 1997;38:302–6.
  • 23. Livingston JC, Chin R, Haddad B, et al. Reductions of vascular endothelial growth factor and PGF concentrations in severe preeclampsia. Am J Obstet Gynecol 2000; 183:1554–57.
  • 24. Akercan F, Cirpan T, Terek MC et al. The immunohistochemical evaluation of VEGF in placenta biopsies of pregnancies complicated by preeclampsia. Arch Gynecol Obstet 2008;277:109–14.
  • 25. Chung JY, Song Y, Wang Y, et al. Differential expression of VEGF, EG-VEGF, and VEGF receptors in human placentas from normal and pre-eclamptic Pregnancies. J Clin Endocrinol Metab 2004;89:2484–90.
  • 26. Koga K, Osuga Y, Yoshino O, et al. Elevated serum soluble vascular endothelial growth factor receptor 1(sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab 2003;88:2348–51.
  • 27. Kurtoglu E, Avci B, Kokcu A, et al. Serum VEGF and PGF may be significant markers in prediction of severity of preeclampsia. J Matern Fetal Neonatal Med 2016; 29: 1987–92.
  • 28. Trollmann R, Amann K, Schoof E, et al. Hypoxia activates the human placental vascular endothelial growth factor system in vitro and in vivo. Am J Obstet Gynecol 2003;188:517–23.
  • 29. Andrade-Scherholz PL, Cristina de Souza P, Spadacci-Morena DD, Godosevicius Katz S. Vimentin is synthesized by mouse vascular trophoblast giant cells from embryonic day 7.5 onwards and is a characteristic factor of these cells. Placenta 2003;34:518–25.
  • 30. Woolf EC, Curley KL, Liu Q, et al. The ketogenic diet alters the hypoxic response and affects expression of proteins associated with angiogenesis, invasive potential and vascular permeability in a mouse glioma model. PLoS ONE 2015;10: e0130357. doi:10.1371/journal.pone.0130357.

Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas

Year 2016, Volume: 43 Issue: 3, 400 - 405, 01.09.2016

Abstract

Objective: In this study, we aimed to investigate the expression levels of vascular endothelial growth factor (VEGF) which stimulates angiogenesis and vimentin, an intermediate cytoskeleton filaments, in both preeclamptic and normotensive placentas. Methods: In this study, placentas after birth in 35-38 weeks were included. Ten preeclamptic placentas and ten normal placentas were used. Tissue pieces which had been soaked in 10% formaldehyde solution were examined histologically after routine paraffin follow. The expression levels of VEGF and vimentin were measured by Western Blot. Results: It was found that syncytial proliferation was in­creased in preeclamptic placentas. Intervillous syncytial knots, syncytial edema, collagen increase and vascular endothelial damage were observed. It was observed that VEGF and vimentin expression levels were increased as a result of preeclampsia. Conclusion: Nonfunctional VEGF which could not bind to its receptor leading to increased VEGF level may lead to inadequate angiogenesis in preeclamptic placenta. In addition, it is thought that an increase in vimentin level in preeclamptic placenta may cause reduced vascular per­meability.

References

  • 1. American College of Obstetricians and Gynecologists. Hypertension in Pregnancy. Obstet Gynecol 2013;122:1122–31.
  • 2. Steegers E, Von Dadelszen P, Duvekot J, Pijnenborg R. Pre-eclampsia. Lancet 2010;376:631–44.
  • 3. Saleh L, Verdonk K, Visser W, et al. The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia. Ther Adv Cardiovasc Dis 2016; DOI: 10.1177/1753944715624853.
  • 4. Sak S, Erdemoğlu M, Ağaçayak E, et al. Evaluation of serum Troponin I Levels in preeclampsia. Dicle Med J 2015;42:186–91
  • 5. Verdonk K, Visser W, Van Den Meiracker A, Danser A. The renin–angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad. Clin Sci (Lond) 2014;126:537–44.
  • 6. Maynard S, Epstein F, Karumanchi S. Pre-eclampsia and angiogenic imbalance. Annu Rev Med 2008;59:61–78.
  • 7. Walentin K, Hinze C, Schmidt-Ott KM. The basal chorionic trophoblast cell layer: An emerging coordinator of placenta development. Bioessays 2016;38:254–65.
  • 8. Davies JE, Pollheimer J, Yong HEJ, et al. Epithelial-mesenchymal transition during extravillous trophoblast differentiation. Cell Adh Migr 2016; DOI: 10.1080/19336918.
  • 9. Patel A and Dash PR. Formation of atypical podosomes in extravillous trophoblasts regulates extracellular matrix degradation. Eur J Cell Biol 2012;91:171–9.
  • 10. Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension 2013;62:1046–54.
  • 11. Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 2014;10:466–80.
  • 12. Zhou Y, Damsky CH, Fisher SJ. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? JClin Invest 1997;99:2152–64.
  • 13. Lee ES, Oh MJ, Jung JW, et al. The levels of circulating vascular endothelial growth factor and soluble Flt-1 in pregnancies complicated by preeclampsia. J Korean Med Sci 2007;22:94–8.
  • 14. Procopciuc LM, Caracostea G, Zaharie G, Stamatian F. Maternal/newborn VEGF-C936T interaction and its influence on the risk, severity and prognosis of preeclampsia, as well as on the maternal angiogenic profile. J Matern Fetal Neonatal Med 2014;27:1754–60.
  • 15. Kalay S, Cakcak B, Oztekin O, et al. The role of VEGF and its soluble receptor VEGFR-1 in preterm newborns of preeclamptic mothers with RDS. J Matern Fetal Neonatal Med 2013;26:978–83.
  • 16. Shirakawa T, Miyahara Y, Kenji Tanimura K, et al. Expression of Epithelial-Mesenchymal Transition-related Factors in Adherent Placenta. Int J Gynecol Pathol 2015;34:584–9.
  • 17. Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 2009;1796:75–90.
  • 18. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom BJOG 2011;118:1–203.
  • 19. Sezer SD, Küçük M, Döger FK, et al. VEGF, PIGF and HIF-1a in placentas of early- and late-onset pre-eclamptic patients. Gynecol Endocrinol 2013;29:797–800.
  • 20. Vuorela P, Hatva E, Lymboussaki A, et al. Expression of vascular endothelial growth factor and placenta growth factor in human placenta. Biol Reprod 1997;56:489–94.
  • 21. Anthony FW, Evans PW, Wheeler T, et al. Variation in detection of VEGF in maternal serum by immunoassay and the possible influence of binding proteins. Ann Clin Biochem 1997;34:276–80.
  • 22. Kupfermine MJ, Daniel Y, Englender T, et al. Vascular endothelial growth factor is increased in patients with preeclampsia. Am J Reprod Immunol 1997;38:302–6.
  • 23. Livingston JC, Chin R, Haddad B, et al. Reductions of vascular endothelial growth factor and PGF concentrations in severe preeclampsia. Am J Obstet Gynecol 2000; 183:1554–57.
  • 24. Akercan F, Cirpan T, Terek MC et al. The immunohistochemical evaluation of VEGF in placenta biopsies of pregnancies complicated by preeclampsia. Arch Gynecol Obstet 2008;277:109–14.
  • 25. Chung JY, Song Y, Wang Y, et al. Differential expression of VEGF, EG-VEGF, and VEGF receptors in human placentas from normal and pre-eclamptic Pregnancies. J Clin Endocrinol Metab 2004;89:2484–90.
  • 26. Koga K, Osuga Y, Yoshino O, et al. Elevated serum soluble vascular endothelial growth factor receptor 1(sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab 2003;88:2348–51.
  • 27. Kurtoglu E, Avci B, Kokcu A, et al. Serum VEGF and PGF may be significant markers in prediction of severity of preeclampsia. J Matern Fetal Neonatal Med 2016; 29: 1987–92.
  • 28. Trollmann R, Amann K, Schoof E, et al. Hypoxia activates the human placental vascular endothelial growth factor system in vitro and in vivo. Am J Obstet Gynecol 2003;188:517–23.
  • 29. Andrade-Scherholz PL, Cristina de Souza P, Spadacci-Morena DD, Godosevicius Katz S. Vimentin is synthesized by mouse vascular trophoblast giant cells from embryonic day 7.5 onwards and is a characteristic factor of these cells. Placenta 2003;34:518–25.
  • 30. Woolf EC, Curley KL, Liu Q, et al. The ketogenic diet alters the hypoxic response and affects expression of proteins associated with angiogenesis, invasive potential and vascular permeability in a mouse glioma model. PLoS ONE 2015;10: e0130357. doi:10.1371/journal.pone.0130357.
There are 30 citations in total.

Details

Other ID JA73GE24GU
Journal Section Research Article
Authors

Sevgi İrtegün This is me

Elif Ağaçayak This is me

Engin Deveci This is me

Publication Date September 1, 2016
Submission Date September 1, 2016
Published in Issue Year 2016 Volume: 43 Issue: 3

Cite

APA İrtegün, S., Ağaçayak, E., & Deveci, E. (2016). Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas. Dicle Medical Journal, 43(3), 400-405.
AMA İrtegün S, Ağaçayak E, Deveci E. Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas. diclemedj. September 2016;43(3):400-405.
Chicago İrtegün, Sevgi, Elif Ağaçayak, and Engin Deveci. “Examining the Expression Level of VEGF and Vimentin by Immunohistochemistry and Western Blot in Preeclamptic and Normotensive Placentas”. Dicle Medical Journal 43, no. 3 (September 2016): 400-405.
EndNote İrtegün S, Ağaçayak E, Deveci E (September 1, 2016) Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas. Dicle Medical Journal 43 3 400–405.
IEEE S. İrtegün, E. Ağaçayak, and E. Deveci, “Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas”, diclemedj, vol. 43, no. 3, pp. 400–405, 2016.
ISNAD İrtegün, Sevgi et al. “Examining the Expression Level of VEGF and Vimentin by Immunohistochemistry and Western Blot in Preeclamptic and Normotensive Placentas”. Dicle Medical Journal 43/3 (September 2016), 400-405.
JAMA İrtegün S, Ağaçayak E, Deveci E. Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas. diclemedj. 2016;43:400–405.
MLA İrtegün, Sevgi et al. “Examining the Expression Level of VEGF and Vimentin by Immunohistochemistry and Western Blot in Preeclamptic and Normotensive Placentas”. Dicle Medical Journal, vol. 43, no. 3, 2016, pp. 400-5.
Vancouver İrtegün S, Ağaçayak E, Deveci E. Examining the expression level of VEGF and vimentin by immunohistochemistry and Western Blot in preeclamptic and normotensive placentas. diclemedj. 2016;43(3):400-5.