Endothelial dysfunction after pregnancy‐induced hypertension

Henriques, Ana; Carvalho, Francisco Herlânio Costa; Feitosa, Helvécio Neves; Macena, Raimunda Hermelinda Maia; Mota, Rosa Maria Salani; Alencar, Júlio César Garcia de

doi:10.1016/j.ijgo.2013.08.016

Cited by 41 publications

(42 citation statements)

References 19 publications

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“…Women with a history of preeclampsia are at higher risk for developing diabetes mellitus,6 stroke,7 and cardiovascular8 and renal diseases9 in later life. This susceptibility to cardiorenal and metabolic diseases post–index pregnancy has been attributed to the pathophysiological mechanisms10, 11 initiated by the placental ischemia. In addition to the maternal effects, preeclampsia is highly associated with intrauterine growth restriction12 and developmentally programs the increased risk for cardiovascular disease,13, 14 stroke,15 renal disease,16 and metabolic dysfunction17, 18 in the adult offspring of preeclamptic women 19.…”

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confidence: 99%

A Maternally Sequestered, Biopolymer‐Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia

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Mahdi

Chapman

et al. 2017

JAHA

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BackgroundPreeclampsia is a hypertensive syndrome that complicates 3% to 5% of pregnancies in the United States. Preeclampsia originates from an improperly vascularized and ischemic placenta that releases factors that drive systemic pathophysiology. One of these factors, soluble fms‐like tyrosine kinase‐1, is believed to sequester vascular endothelial growth factor (VEGF), leading to systemic endothelial dysfunction and hypertension. With the goal of targeting soluble fms‐like tyrosine kinase‐1 while simultaneously preventing fetal exposure to VEGF, we fused VEGF to elastin‐like polypeptide, a biopolymer carrier that does not cross the placental barrier (ELP‐VEGF).Methods and Results ELP‐VEGF restored in vitro endothelial cell tube formation in the presence of plasma from placental ischemic rats. Long‐term administered ELP‐VEGF in pregnant rats accumulated in maternal kidneys, aorta, liver, and placenta, but the protein was undetectable in the pups when administered at therapeutic doses in dams. Long‐term administration of ELP‐VEGF in a placental ischemia rat model achieved dose‐dependent attenuation of hypertension, with blood pressure equal to sham controls at a dose of 5 mg/kg per day. ELP‐VEGF infusion increased total plasma soluble fms‐like tyrosine kinase‐1 levels but dramatically reduced free plasma soluble fms‐like tyrosine kinase‐1 and induced urinary excretion of nitrate/nitrite, indicating enhanced renal nitric oxide signaling. ELP‐VEGF at up to 5 mg/kg per day had no deleterious effect on maternal or fetal body weight. However, dose‐dependent adverse events were observed, including ascites production and neovascular tissue encapsulation around the minipump.Conclusions ELP‐VEGF has the potential to treat the preeclampsia maternal syndrome, but careful dosing and optimization of the delivery route are necessary.

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confidence: 99%

A Maternally Sequestered, Biopolymer‐Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia

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Mahdi

Chapman

et al. 2017

JAHA

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“…However, after the AG490 injection, p/t-JAK2, p/t-STAT3 and SOCS1 expressions were downregulated. PIH causes the release of anti-angiogenic factors into the mother's circulation, resulting in endothelial injury [2,3]. Previous studies demonstrated that the combined treatment of anti-placental growth factor (PLGF) and vascular endothelial growth factor A (VEGF-A) could reduce ocular hemangiomas growth and choroidal neovascularization [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, this high-incidence disease of pregnant women can damage the brain, heart, kidney and other human organs [2]. PIH has been correlated with aberrant placentation, which leads to the release of anti-angiogenic factors into the mother's circulation, resulting in endothelial injury as well as maternal and fetal damage [3]. PIH induces a wide variety of disorders, such as gestational hypertension, preeclampsia and eclampsia [4].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension

Luo

et al. 2016

Cell Physiol Biochem

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Background/Aims: The present study aimed to investigate the effects of the JAK2/STAT3/SOSC1 signaling pathway on the secretion function of vascular endothelial cells (VECs) in a rat model of pregnancy-induced hypertension (PIH). Methods: A PIH rat model was established. Forty-eight pregnant Sprague-Dawley female rats were selected and assigned into four groups: the normal group (normal non-pregnant rats), the non-PIH group (pregnant rats without PIH), the PIH group (pregnant rats with PIH) and the AG490 group (pregnant rats with PIH treated with AG490). Systolic blood pressure (SBP) and urinary protein (UP) were measured. The expressions of JAK2/STAT3/SOSC1 signaling pathway-related proteins in placenta tissues were detect by Western blotting. Radioimmunoassay was applied to detect serum levels of nitric oxide (NO), super oxide dismutase (SOD), placental growth factor (PGF), thromboxane B2 (TXB2) and endothelin (ET). Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Results: Compared with the normal and non-PIH groups, the PIH and AG490 groups had higher SBP and UP levels at 17^th and 25^th day of pregnancy. The expressions of p/t-JAK2, p/t-STAT3 and SOSC1 in the PIH and AG490 groups were higher than those in the non-PIH group, while the expressions of p/t-JAK2, p/t-STAT3 and SOSC1 in the AG490 group were lower than those in the PIH group. Compared with the non-PIH group, serum levels of ET, TXB2, IL-6 and TNF-α were increased in the PIH and AG490 groups, while serum levels of NO, SOD, 6-keto-PGF1a and IL-10 levels were reduced. Furthermore, the AG490 had lower serum levels of ET, TXB2, IL-6 and TNF-α and higher serum levels of NO, SOD, 6-keto-PGF1a and IL-10 than those in the PIH group. Conclusion: Our study provides evidence that inhibition of the JAK2/STAT3/SOSC1 signaling pathway could improve the secretion function of VECs in PIH rats.

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“…There are complications of the fetus and newborn associated with hypertension at 140/90 mm Hg and higher [1,5,7]. Mechanisms of increased blood pressure, leading to hypertension and/or strengthening of symptoms during pregnancy are very diverse.…”

Section: Introductionmentioning

confidence: 99%

Instrumental and Diagnostic Criteria of Hemodynamic Disorders and Endothelial Dysfunction Correction in Pregnants With Arterial Hypertension

Heryak

Humenna²

2014

IJMMR

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Endothelial dysfunction after pregnancy‐induced hypertension

Abstract: Women with a history of PIH were found to have a higher frequency of long-term endothelial dysfunction.

Cited by 41 publications

References 19 publications

A Maternally Sequestered, Biopolymer‐Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia

A Maternally Sequestered, Biopolymer‐Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia

Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension

Instrumental and Diagnostic Criteria of Hemodynamic Disorders and Endothelial Dysfunction Correction in Pregnants With Arterial Hypertension

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