Dataset Information

Placental growth factor blunts uterine artery responses to angiotensin II.

ABSTRACT:

Objective

Changes in maternal serum concentration of placental growth factor (PlGF) and vascular response to intravascular infusion of Angiotensin II (Ang II) follow a bell-shaped curve pattern during gestation. This study evaluates the effects of PlGF and soluble vascular endothelial growth factor receptor-1 (sFlt-1) on responses of human uterine arteries (UA) to Ang II.

Design

Experimental.

Setting

Baylor College of Medicine and Texas Children's Hospital-Pavilion for Women.

Sample

Uterine arteries samples (n = 14) were obtained from normotensive women undergoing caesarean hysterectomy at ?32 weeks.

Methods

Uterine arteries rings were incubated with (1) Krebs solution; (2) PlGF at 1.45, 14.5, and 500 pg/ml; (3) sFlt-1 at 2 ng/ml; and (4) a combination of sFlt-1, and PlGF. Dose-contraction responses to Ang II were determined in UA rings incubated in the above-mentioned conditions. Responses were also measured in presence of L-NAME or inhibitors of endothelium-derived hyperpolarising factor: apamine and charybdotoxin. The t-test was used for comparisons.

Main outcome measure

Changes in vascular reactivity of UA rings.

Results

PlGF blunted (P = 0.03) and sFlt-1 increased (P <0.01) the UA maximum responses to Ang II. A combination of sFlt-1 and PlGF blunted UA responses to Ang II (P < 0.05). l-NAME, apamine, and charybdotoxin reversed the relaxation effects of PlGF on UA responses to Ang II (P < 0.05).

Conclusions

PlGF contributes to the blunted vascular response to Angiotensin II during normotensive pregnancies and sFlt-1 appears to attenuate this effect. PlGF and sFlt-1 may contribute to the regulation of vascular tone during pregnancy by altering the vascular response to Angiotensin II.

Funding

Baylor College of Medicine.

Tweetable abstract

Placental growth factor and soluble vascular endothelial growth factor receptor-1 modulate the uterine artery response to Angiotensin II in normotensive pregnant women.

SUBMITTER: Espinoza J

PROVIDER: S-EPMC7004274 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Placental growth factor blunts uterine artery responses to angiotensin II.

Espinoza J J Betancourt A A Belfort M A MA Shamshirsaz A A AA Fox K A KA Yallampalli C C

BJOG : an international journal of obstetrics and gynaecology 20190318 8

<h4>Objective</h4>Changes in maternal serum concentration of placental growth factor (PlGF) and vascular response to intravascular infusion of Angiotensin II (Ang II) follow a bell-shaped curve pattern during gestation. This study evaluates the effects of PlGF and soluble vascular endothelial growth factor receptor-1 (sFlt-1) on responses of human uterine arteries (UA) to Ang II.<h4>Design</h4>Experimental.<h4>Setting</h4>Baylor College of Medicine and Texas Children's Hospital-Pavilion for Wome ...[more]

PMID: 30771259

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Project description:We previously showed that advancing the increase in estradiol levels from the second to the first third of baboon pregnancy suppressed placental extravillous trophoblast (EVT) invasion and remodeling of the uterine spiral arteries. Cell culture studies show that vascular endothelial cell growth factor (VEGF) plays a central role in regulating EVT migration and remodeling of the uterine spiral arteries by increasing the expression/action of certain integrins that control extracellular matrix remodeling. To test the hypothesis that the estradiol-induced reduction in vessel remodeling in baboons is associated with an alteration in VEGF and integrin expression, extravillous placental VEGF and integrin expression was determined on d 60 of gestation (term is 184 d) in baboons in which uterine artery transformation was suppressed by maternal estradiol administration on d 25-59. EVT uterine spiral artery invasion was 5-fold lower (P < 0.01), and VEGF protein expression, quantified by in situ proximity ligation assay, was 50% lower (P < 0.05) in the placenta anchoring villi of estradiol-treated than in untreated baboons. α1β1 and α5β1 mRNA levels in cells isolated by laser capture microdissection from the anchoring villi and cytotrophoblastic shell of estradiol-treated baboons were over 2-fold (P < 0.01) and 40% (P < 0.05) lower, respectively, than in untreated animals. In contrast, placental extravillous αvβ3 mRNA expression was unaltered by estradiol treatment. In summary, extravillous placental expression of VEGF and α1β1 and α5β1 integrins was decreased in a cell- and integrin-specific manner in baboons in which EVT invasion and remodeling of the uterine spiral arteries were suppressed by prematurely elevating estradiol levels in early pregnancy. We propose that estrogen normally controls the extent to which the uterine arteries are transformed by placental EVT in primate pregnancy by regulating expression of VEGF and particular integrin extracellular remodeling molecules that mediate this process.

Dataset Information

Placental growth factor blunts uterine artery responses to angiotensin II.

Objective

Design

Setting

Sample

Methods

Main outcome measure

Results

Conclusions

Funding

Tweetable abstract

Publications

Placental growth factor blunts uterine artery responses to angiotensin II.

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