Relation between Circulating Angiotensin II Type 1 Receptor Agonistic Autoantibodies and Soluble fms-Like Tyrosine Kinase 1 in the Pathogenesis of Preeclampsia

Stepan, Holger; Faber, R.; Wessel, Niels; Wallukat, Gerd; Schultheiss, Heinz‐Peter; Walther, Thomas

doi:10.1210/jc.2005-2698

Cited by 49 publications

(41 citation statements)

References 15 publications

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“…Furthermore, the renin-angiotensin system, either through angiotensin II or angiotensin II receptor type 1-auto antibody, may also be a contributing factor, although this appears to be more contentious based on recent findings in the human literature. 32 Alternatively, the present work suggests that VEGF supplementation may hold potential as a possible intervention in preeclamptic pregnancies. Lastly, we feel that the present work provides a platform from which other studies may be launched to elucidate underlying mechanisms and to develop efficacious interventions for preeclampsia.…”

Section: Perspectivesmentioning

confidence: 76%

Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats Is Associated With Increased Soluble Fms-Like Tyrosine Kinase-1 Expression

2007

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Abstract-The balance between proangiogenic and antiangiogenic factors, such as vascular endothelial growth factor, placental growth factor, and soluble fms-like tyrosine kinase-1 (sFlt-1), is altered in preeclampsia, and this dysregulation of angiogenic factors may be important in the pathogenesis of preeclampsia. Although sFlt-1 is elevated in preeclampsia, the mechanisms responsible for increasing this antiangiogenic factor remain unclear. We hypothesized that the hypertension produced by reduced uterine perfusion pressure (RUPP) is associated with increased sFlt-1 expression and decreased plasma vascular endothelial growth factor and placental growth factor concentrations in the pregnant rat. Arterial pressure was increased (130Ϯ3 versus 100Ϯ2 mm Hg; PϽ0.01) in the RUPP rats compared with the normal pregnant control rats. Plasma sFlt-1 concentration (660Ϯ270 versus 82Ϯ26 pg/mL; PϽ0.05) was increased, whereas plasma free placental growth factor (0.28Ϯ0.05 versus 1.7Ϯ0.5 pg/mL; PϽ0.01) and vascular endothelial growth factor (594Ϯ34 versus 830Ϯ33 pg/mL; PϽ0.01) concentrations were decreased in the RUPP rats compared with normal pregnant rats. Plasma sFlt-1:placental growth factor (37.2Ϯ7.8 versus 8.9Ϯ1.6; PϽ0.02) and sFlt-1:vascular endothelial growth factor (0.86Ϯ0.22 versus 0.28Ϯ0.06; PϽ0.05) ratios were increased in the RUPP rats compared with normal pregnant rats. Immunoreactive placental sFlt-1 was increased (1.1Ϯ0.1 versus 0.3Ϯ0.1; PϽ0.01) in RUPP rats contrasted with the normal pregnant rats. These findings support our hypothesis that RUPP increases the expression of sFlt-1 and alters the balance of angiogenic factors in the maternal circulation. These data also indicate that the RUPP model of pregnancy-induced hypertension may provide an invaluable model for mechanistic studies into the role of sFlt-1 in the pathogenesis preeclampsia. Key Words: preeclampsia Ⅲ gestation Ⅲ VEGF Ⅲ blood pressure Ⅲ angiogenic P regnancy-induced hypertension (PIH), or preeclampsia, is a major obstetric problem and a significant source of maternal and neonatal morbidity and mortality. 1 Although PIH continues to affect Ϸ8% of all pregnancies, the incidence of preeclampsia has seen a 40% increase in recent years. 2 Although PIH has been well characterized, with many studies indicating that proteinuria, edema, endothelial cell dysfunction, and insufficient placentation are all hallmarks of this disorder, 3,4 the mechanisms underlying the pathogenesis of this dreaded condition remain obscure. The continuing uncertainties regarding the mechanisms underlying the pathogenesis of preeclampsia are at least in part attributable to the difficulties in performing mechanistic studies in pregnant women. 5,6 Thus, the continued characterization and development of animal models for mechanistic research of preeclampsia remains an important endeavor.Recent studies have reported the existence of an imbalance between proangiogenic and antiangiogenic factors, such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and ...

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Section: Perspectivesmentioning

confidence: 76%

Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats Is Associated With Increased Soluble Fms-Like Tyrosine Kinase-1 Expression

2007

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“…[73][74][75][76][77][78][79][80] Recently, studies have reported that increased sFlt-1 may have a predictive value in diagnosing preeclampsia as concentrations seem to increase before manifestation of overt symptoms (eg, hypertension, proteinuria). 73,[81][82][83][84] In an elegantly designed study reported several years ago, Maynard et al 85 reported that exogenous administration of sFlt-1 into pregnant rats via adenovirus mediated gene transfer resulted in increased arterial pressure and proteinuria, and decreased plasma free VEGF and PlGF concentrations similar to that observed in the preeclamptic patients. Subsequently, similar observations using adenovirus transfection have been reported in the mouse.…”

Section: Angiogenic Factorsmentioning

confidence: 90%

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

2008

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“…Furthermore, AT1-AA stimulates sFlt-1 and sEng by inducing TNF-a and overcoming its negative regulator, HO (59). In terms of human studies, Stepan et al (60) did not find a correlation between AT1-AA and sFlt-1 levels, whereas Siddiqui et al (61) did. Given these mixed results in humans, it remains questionable whether AT1-AA and sFlt-1 levels share the same pathophysiologic mechanism.…”

Section: Angiotensin Receptor 1 Autoantibodiesmentioning

confidence: 98%

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps

Prasanna

Brima

et al. 2016

CJASN

510

328

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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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Relation between Circulating Angiotensin II Type 1 Receptor Agonistic Autoantibodies and Soluble fms-Like Tyrosine Kinase 1 in the Pathogenesis of Preeclampsia

Cited by 49 publications

References 15 publications

Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats Is Associated With Increased Soluble Fms-Like Tyrosine Kinase-1 Expression

Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats Is Associated With Increased Soluble Fms-Like Tyrosine Kinase-1 Expression

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

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