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George EM, Stout JM, Stec DE, et al. Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents. Front Pharmacol. 2015;6:165doi: 10.3389/fphar.2015.00165.
George, E. M., Stout, J. M., Stec, D. E., & Granger, J. P. (2015). Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents. Frontiers in pharmacology, 6165. https://doi.org/10.3389/fphar.2015.00165
George, Eric M, et al. "Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents." Frontiers in pharmacology vol. 6 (2015): 165. doi: https://doi.org/10.3389/fphar.2015.00165
George EM, Stout JM, Stec DE, Granger JP. Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents. Front Pharmacol. 2015 Aug 17;6:165. doi: 10.3389/fphar.2015.00165. eCollection 2015. PMID: 26347650; PMCID: PMC4538306.
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Front Pharmacol. 2015 Aug 17;6:165. doi: 10.3389/fphar.2015.00165. eCollection 2015.

Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents.

Frontiers in pharmacology

Eric M George, Jacob M Stout, David E Stec, Joey P Granger

Affiliations

  1. Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, MS, USA ; Department of Biochemistry, University of Mississippi Medical Center , Jackson, MS, USA.
  2. Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, MS, USA.

PMID: 26347650 PMCID: PMC4538306 DOI: 10.3389/fphar.2015.00165

Abstract

Pre-eclampsia is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti-angiogenic protein, sFlt-1, and inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Previous studies have demonstrated that heme oxygenase (HO) induction can block TNF-α pathways in vitro and attenuate placental ischemia-induced sFlt-1 in vivo. Here, we investigated whether HO-1 induction could attenuate TNF-α-induced hypertension in pregnant rats. In response to TNF-α infusion (100 ng/day i.p.), maternal mean arterial pressure (MAP) increased vs. control animals (104 ± 3 vs. 119 ± 3 mmHg). HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-α-infused animals (108 ± 2 mmHg). Placental vascular endothelial growth factor (VEGF) was decreased in response to TNF-α infusion (92 ± 4 vs. 76 ± 2 pg/mg). Placental sFlt-1 was increased by TNF-α infusion (758 ± 45 vs. 936 ± 46 pg/mg, p < 0.05), which trended to normalization by HO-1 induction (779 ± 98 pg/mg). In contrast, HO-1 induction had no significant effect on placental VEGF in TNF-α-infused animals. Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1. Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted.

Keywords: TNF-α; VEGF; heme oxygenase; pre-eclampsia; sFlt-1

References

  1. Hypertension. 2001 Aug;38(2):210-5 - PubMed
  2. Hypertension. 2012 Aug;60(2):507-11 - PubMed
  3. J Clin Invest. 2003 Mar;111(5):649-58 - PubMed
  4. Clin Ther. 2014 Dec 1;36(12 ):1873-81 - PubMed
  5. Hypertension. 2008 Dec;52(6):1161-7 - PubMed
  6. Am J Obstet Gynecol. 1998 Mar;178(3):562-7 - PubMed
  7. Circulation. 2007 Apr 3;115(13):1789-97 - PubMed
  8. Am J Obstet Gynecol. 1994 Jun;170(6):1752-7; discussion 1757-9 - PubMed
  9. Hypertension. 2004 Jun;43(6):1221-6 - PubMed
  10. Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1495-500 - PubMed
  11. Int J Biochem Cell Biol. 2009 May;41(5):1025-33 - PubMed
  12. Am J Hypertens. 2002 Feb;15(2 Pt 1):170-5 - PubMed
  13. Obstet Gynecol. 2013 Nov;122(5):1122-31 - PubMed
  14. Curr Pharm Des. 2014;20(9):1318-27 - PubMed
  15. J Nutr Biochem. 2012 Sep;23 (9):1134-45 - PubMed
  16. Am J Physiol Regul Integr Comp Physiol. 2010 Oct;299(4):R1044-9 - PubMed
  17. Mol Med. 2000 May;6(5):391-409 - PubMed
  18. Hypertension. 2011 May;57(5):941-8 - PubMed
  19. Hypertension. 2006 Oct;48(4):711-6 - PubMed
  20. Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1472-8 - PubMed
  21. Hypertension. 2005 Jul;46(1):82-6 - PubMed
  22. Am J Pathol. 1997 Dec;151(6):1809-18 - PubMed
  23. Kidney Int. 2005 Dec;68(6):2745-55 - PubMed
  24. Int J Hypertens. 2012;2012:486053 - PubMed
  25. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99 - PubMed
  26. J Soc Gynecol Investig. 2003 Feb;10(2):82-93 - PubMed
  27. Am J Hypertens. 2013 Jul;26(7):918-23 - PubMed
  28. Br J Obstet Gynaecol. 1995 Jan;102(1):20-5 - PubMed

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