Hydrogen sulfide producing enzymes in pregnancy and preeclampsia

Holwerda, Kim M.; Bos, Eelke M.; Rajakumar, Augustine; Ris‐Stalpers, Carrie; Pampus, Maria G. van; Timmer, Albertus; Erwich, Johannes; Faas, Marijke M.; Goor, van Harry; Lely, A. Titia

doi:10.1016/j.placenta.2012.02.014

Cited by 69 publications

(50 citation statements)

References 24 publications

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“…52 Interestingly, the expression of CBS and CSE in women with preeclampsia is decreased in the placenta. 47,48 The administration of H 2 S had the same effect on sFlt1 levels in pregnant rats, compared with nonpregnant rats (data not shown). Importantly, pups from NaHS-treated mothers showed no apparent dysmorphic characteristics and there were no adverse effects of NaHS on placental and pup weight (Supplemental Figure 3).…”

Section: Discussionmentioning

confidence: 82%

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Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

Holwerda¹,

Burke²,

Faas³

et al. 2014

Journal of the American Society of Nephrology

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Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein, is elevated in kidney diseases and contributes to the development of preeclampsia. Hydrogen sulfide is a vasorelaxant and proangiogenic gas with therapeutic potential in several diseases. Therefore, we evaluated the potential therapeutic effect and mechanisms of action of hydrogen sulfide in an animal model of sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis created by adenovirus-mediated overexpression of sFlt1 in Sprague-Dawley rats. We injected sFlt1-overexpressing animals intraperitoneally with the hydrogen sulfide-donor sodium hydrosulfide (NaHS) (50 mmol/kg, twice daily) or vehicle (n=7 per group). Treatment with NaHS for 8 days significantly reduced sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis. Measurement of plasma protein concentrations with ELISA revealed a reduction of free plasma sFlt1 and an increase of free plasma vascular endothelial growth factor (VEGF) after treatment with NaHS. Renal VEGF-A mRNA expression increased significantly with NaHS treatment. In vitro, NaHS was proangiogenic in an endothelial tube assay and attenuated the antiangiogenic effects of sFlt1. Stimulation of podocytes with NaHS resulted in both short-term VEGF release (120 minutes) and upregulation of VEGF-A mRNA levels (24 hours). Furthermore, pretreatment of mesenteric vessels with a VEGF receptor 2-neutralizing antibody significantly attenuated NaHS-induced vasodilation. These results suggest that hydrogen sulfide ameliorates sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis in rats by increasing VEGF expression. Further studies are warranted to evaluate the role of hydrogen sulfide as a novel therapeutic agent for vascular disorders such as preeclampsia.

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Section: Discussionmentioning

confidence: 82%

“…47,48 Preeclampsia is associated with elevated levels of homocysteine, a key protein in the trans-sulfurization Figure 4. Effect of NaHS on sFlt1 and VEGF expression in rats.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

Holwerda¹,

Burke²,

Faas³

et al. 2014

Journal of the American Society of Nephrology

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“…Clinically, the rats showed decreased proteinuria, hypertension, and glomerular injury (38). Conversely, decreased levels of the precursor molecules of H 2 S have been found in patients with preeclampsia (37,39,40). Chronic administration of a cystathionine g-lyase inhibitor, DL-propargylglycine, to pregnant mice resulted in elevated mean BP, liver damage, and decreased fetal growth.…”

Section: Hydrogen Sulfide Pathwaymentioning

confidence: 99%

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps

Prasanna

Brima

et al. 2016

CJASN

459

313

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Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a selflimited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

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“…[8][9][10][11][12] The aim of this review is to give an overview of the role of gasotransmitters in the physiology of pregnancy and relate their aberrant production to preeclampsia. Specific emphasis will be put on and overview their therapeutic potential for preeclampsia.…”

mentioning

confidence: 99%

“…10,33 In the placenta, these enzymes are active (both rat and human) and are able to produce H 2 S. 6 The catalytic activity of placental CBS was also shown by incubation of human placental explants with increasing homocysteine concentrations leading to elevated CBS activity and increased cysteine in vitro. 34 In the human fetoplacental circulation, H 2 S mediates vasodilatation in vitro via K ATP channels and by interaction with NO.…”

mentioning

confidence: 99%