Endogenous cardiotonic steroids and vascular fibrosis in preeclampsia
https://doi.org/10.18705/1607-419X-2018-24-6-684-692
Abstract
Background. Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis.
Objective. We hypothesized that in human and rat PE, elevated MBG level is associated with development of fibrosis of umbilical arteries and rat thoracic aortae.
Design and methods. Twelve patients with PE (mean blood pressure (BP) 118 ± 4 mmHg; mean age 28 ± 2 years; mean gestation age 36 ± 1 weeks) and 12 gestational age-matched normal pregnant subjects (mean BP 92 ± 2 mmHg; mean age 26 ± 1 years; mean gestation age 37 ± 1 weeks) were enrolled in the clinical study. We tested 16 pregnant Sprague-Dawley rats. Hypertension was provoked in 8 rats by 1,8 % Na supplementation.
Results. PE in humans and rats was associated with the higher plasma MBG level and was associated with five-fold decrease in Fli-1 level and four-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (p < 0,01). Isolated rings of umbilical arteries from the subjects with PE exhibited impaired response to the relaxant effect of sodium nitroprusside vs. control vessels (EC50 = 141 nmol/L vs. EC50 = 0,9 nmol/L; p < 0,001). Similar results were obtained for thoracic aorta of rats with experimental PE.
Conclusions. These results demonstrate that elevated MBG level is implicated in the development of fibrosis umbilical arteries in PE.
Supporting agencies: Grant № 18–15–00222 “Fundamental research and scientific studies by the individual research groups”
About the Authors
N. I. Agalakova
Sechenov Institute of Evolutionary Physiology and Biochemistry.
Natalia I. Agalakova, PhD in Biology Sciences, Leading Researcher, Sechenov Institute of Evolutionary Physiology and Biochemistry.
Natalia I. Agalakova, PhD in Biology Sciences, Leading Researcher, Sechenov Institute of Evolutionary Physiology and Biochemistry.
V. A. Reznik
Saint Petersburg State Pediatric Medical University.
Vitaly A. Reznik, MD, PhD, Associate Professor, Department of Obstetrics and Gynecology.
Vitaly A. Reznik, MD, PhD, Associate Professor, Department of Obstetrics and Gynecology.
O. V. Nadei
Sechenov Institute of Evolutionary Physiology and Biochemistry.
Olga V. Nadei, Student, St. Petersburg State University.
Olga V. Nadei, Student, St. Petersburg State University.
I. A. Ershov
Saint Petersburg State Pediatric Medical University.
Ivan A. Ershov, MD, Fellow, Department of Obstetrics and Gynecology.
Ivan A. Ershov, MD, Fellow, Department of Obstetrics and Gynecology.
O. S. Rassokha
Saint Petersburg State Pediatric Medical University.
Olga S. Rassokha, Student, Department of Obstetrics and Gynecology.
Olga S. Rassokha, Student, Department of Obstetrics and Gynecology.
M. L. Vasyutina
Almazov National Medical Research Centre.
Marina L. Vasyutina, DVM, Chief Veterinary Officer, Institute of Experimental Medicine.
Marina L. Vasyutina, DVM, Chief Veterinary Officer, Institute of Experimental Medicine.
N. I. Tapilskaya
St Petersburg State Pediatric Medical University; D. O. Ott Obstetrics and Gynecology Research Centre.
Natalia I. Tapilskaya, MD, PhD, Leading Researcher, Department of Reproductive Technologies, Ott Research Institute of Obstetrics, Gynecology and Reproductology, Professor, Department of Obstetrics and Gynecology, Saint Petersburg State Pediatric Medical University.
Natalia I. Tapilskaya, MD, PhD, Leading Researcher, Department of Reproductive Technologies, Ott Research Institute of Obstetrics, Gynecology and Reproductology, Professor, Department of Obstetrics and Gynecology, Saint Petersburg State Pediatric Medical University.
N. N. Rukhliada
Saint Petersburg State Pediatric Medical University.
Nikolai N. Rukhliada, MD, PhD, Associate Professor, Chief, Department of Obstetrics and Gynecology.
Nikolai N. Rukhliada, MD, PhD, Associate Professor, Chief, Department of Obstetrics and Gynecology.
M. M. Galagudza
Almazov National Medical Research Centre.
Michael M. Galagudza, MD, PhD, DSc, Professor, Director, Institute of Experimental Medicine.
Michael M. Galagudza, MD, PhD, DSc, Professor, Director, Institute of Experimental Medicine.
A. Y. Bagrov
Sechenov Institute of Evolutionary Physiology and Biochemistry.
Alexei Y. Bagrov, MD, DSc, Principal Scientist, Sechenov Institute of Evolutionary Physiology and Biochemistry.
Alexei Y. Bagrov, MD, DSc, Principal Scientist, Sechenov Institute of Evolutionary Physiology and Biochemistry.
References
1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785-99. DOI: 10.1016/S0140-6736(05)17987-2
2. Graves SW, Williams GH. Endogenous digitalis-like natriuretic factors. Annu Rev Med. 1987;38:433-44. Review. PubMed PMID: 3034137.
3. Fedorova OV, Bagrov AY. Inhibition of Na/K ATPase from rat aorta by two Na/K pump inhibitors, ouabain and marinobufagenin: evidence of interaction with different alpha-subunit isoforms. Am J Hypertens. 1997 Aug;10(8):929-35. PubMed PMID: 9270089
4. Bagrov AY, Shapiro JI, Fedorova OV. Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets. Pharmacol Rev. 2009 Mar;61(1):9-38. doi: 10.1124/pr.108.000711. Review. PubMed PMID: 19325075; PubMed Central PMCID: PMC2763610.
5. Adesanya CO, Anjorin FI, Sada IA, Parry EH, Sagnella GA, MacGregor GA. Atrial natriuretic peptide, aldosterone, and plasma renin activity in peripartum heart failure. Br Heart J. 1991 Mar;65(3):152-4. PubMed PMID: 1826604; PubMed Central PMCID: PMC1024538.
6. Averina IV, Tapilskaya NI, Reznik VA, Frolova EV, Fedorova OV, Lakatta EG, Bagrov AY. Endogenous Na/K-ATPase inhibitors in patients with preeclampsia. Cell Mol Biol (Noisy-le-grand). 2006 Dec 30;52(8):19-23. PubMed PMID: 17535731.
7. Lopatin DA, Ailamazian EK, Dmitrieva RI, Shpen VM, Fedorova OV, Doris PA, Bagrov AY. Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia. J Hypertens. 1999 Aug;17(8):1179-87. PubMed PMID: 10466474.
8. Fedorova OV, Simbirtsev AS, Kolodkin NI, Kotov AY, Agalakova NI, Kashkin VA, Tapilskaya NI, Bzhelyansky A, Reznik VA, Frolova EV, Nikitina ER, Budny GV, Longo DL, Lakatta EG, Bagrov AY. Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension. J Hypertens. 2008 Dec;26(12):2414-25. doi: 10.1097/HJH.0b013e328312c86a. PubMed PMID: 19008721;PubMed Central PMCID: PMC2583455.
9. Nikitina ER, Mikhailov AV, Nikandrova ES, Frolova EV, Fadeev AV, Shman VV, Shilova VY, Tapilskaya NI, Shapiro JI, Fedorova OV, Bagrov AY. In preeclampsia endogenous cardiotonic steroids induce vascular fibrosis and impair relaxation of umbilical arteries. J Hypertens. 2011 Apr;29(4):769-76. doi: 10.1097/HJH.0b013e32834436a7. PubMed PMID: 21330936; PubMed Central PMCID: PMC3053428.
10. Fedorova OV, Emelianov IV, Bagrov KA, Grigorova YN, Wei W, Juhasz O, Frolova
11. EV, Marshall CA, Lakatta EG, Konradi AO, Bagrov AY. Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists. J Hypertens. 2015 Aug;33(8):1602-10. doi: 10.1097/HJH.0000000000000591. PubMed PMID: 26136067; PubMed Central PMCID: PMC4547457.
12. National Institutes of Health Working Group on Hypertension in Pregnancy. Classification of hypertensive disorders of pregnancy. Bethesda, MD, US Dept. of Health and Human Services, 1991.
13. Haller ST, Kennedy DJ, Shidyak A, Budny GV, Malhotra D, Fedorova OV, Shapiro JI, Bagrov AY. Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure. Am J Hypertens. 2012 Jun;25(6):690-6. doi: 10.1038/ajh.2012.17. Epub 2012 Mar 1. PubMed PMID: 22378033; PubMed Central PMCID: PMC3355226.
14. Xie Z, Askari A. Na(+)/K(+)-ATPase as a signal transducer. Eur J Biochem. 2002 May;269(10):2434-9. PubMed PMID: 12027880.
15. de Wardener HE, He FJ, MacGregor GA. Plasma sodium and hypertension. Kidney
16. Int. 2004 Dec;66(6):2454-66. Review. PubMed PMID: 15569339.
17. Anderson DE, Fedorova OV, Morrell CH, Longo DL, Kashkin VA, Metzler JD, Bagrov AY, Lakatta EG. Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives. Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294(4):R1248-54. doi: 10.1152/ajpregu.00782.2007. Epub
18. 20. PubMed PMID: 18287222; PubMed Central PMCID: PMC2430746.
19. Gonick HC, Ding Y, Vaziri ND, Bagrov AY, Fedorova OV. Simultaneous measurement of marinobufagenin, ouabain, and hypertension-associated protein in various disease states. Clin Exp Hypertens. 1998 Jul-Aug;20(5-6):617-27. PubMed PMID: 9682918.
20. Elkareh J, Periyasamy SM, Shidyak A, Vetteth S, Schroeder J, Raju V, Hariri IM, El-Okdi N, Gupta S, Fedorova L, Liu J, Fedorova OV, Kahaleh MB, Xie Z, Malhotra D, Watson DK, Bagrov AY, Shapiro JI. Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. Am J Physiol Renal Physiol. 2009 May;296(5):F1219-26. doi: 10.1152/ajprenal.90710.2008. Epub 2009 Mar 4. PubMed PMID: 19261738; PubMed Central PMCID: PMC2681369.
Review
For citations:
Agalakova N.I., Reznik V.A., Nadei O.V., Ershov I.A., Rassokha O.S., Vasyutina M.L., Tapilskaya N.I., Rukhliada N.N., Galagudza M.M., Bagrov A.Y. Endogenous cardiotonic steroids and vascular fibrosis in preeclampsia. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2018;24(6):684-692. (In Russ.) https://doi.org/10.18705/1607-419X-2018-24-6-684-692
Views:
1594
Email this article 