Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy

A Rajakumar

AG Gilman

Asma Khalil

C Celik-Ozenci

C Hornig

CM Failla

D Maglione

DE Clark

E Bujold

Eric Jauniaux

FM Belgore

G Falkay

G Viglietto

GA Head

H Roy

J Szelenyi

JM Roberts

K Morishita

K Wakiya

Kevin Harrington

M Henning

M Hollborn

MA Brown

MD Day

P Vuorela

PA Van Zwieten

Pisake Lumbiganon

R Romero

R Tordjman

RJ Levine

RL Kendall

S Ahmad

S Rana

S Venkatesha

SE Maynard

Shanthi Muttukrishna

SP Bottari

U Raab

V Muthig

Y He

ZP Khan

PLoS ONE

English

PubMed

Background: Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy.



Methodology/Principal Findings: In a study conducted at University College Hospital and the Homerton University Hospital in London, we recruited 51 women with PE, 29 with gestational hypertension (GH), and 80 matched normotensive controls. Eight (16%) of the women with PE had severe disease. Placental samples were obtained from a further 48 women (14 PE, 10 GH and 24 matched controls). Serum levels of angiogenic factors were measured before and 24–48 hours after commencing antihypertensive therapy with alpha methyldopa for clinical indications. The same parameters were measured in placental extracts. In both PE (P,0.0001) and GH (P,0.05), serum sFlt-1 was increased and PlGF reduced at all gestations (P,0.001) compared to controls. Serum sEng levels were also increased in PE. Placental concentration of sFlt-1 and sEng was significantly higher in women with PE compared to controls and women with GH (P,0.0001). The concentration of PlGF was significantly lower in the placental tissue of women with PE compared to GH (P = 0.008). Antihypertensive treatment was associated with a significant fall in serum and placental content of sFlt1 and sEng in PE only.



Conclusions: Our data suggest that alpha methyldopa may have a specific effect on placental and/or endothelial cell

function in pre-eclampsia patients, altering angiogenic proteins

Khalil, A

Muttukrishna, S

Harrington, K

Jauniaux, E

St George's Online Research Archive

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Central imidazoline- and alpha 2-receptors involved in the cardiovascular actions of centrally acting antihypertensive agents.

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Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor.

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Placenta growth factor is induced in human keratinocytes during wound healing.

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Role of alpha adrenoceptors in hypertension and in antihypertensive drug treatment.

Rubenson A

The classification and diagnosis of the hypertensive disorders of pregnancy: statement from

The mechanism of the antihypertensive action of -methyldopa in hypertensive rats.

Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14.

Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice.

Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines.

Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders.

Crossref

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

UCL Discovery

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy. = 0.008). Antihypertensive treatment was associated with a significant fall in serum and placental content of sFlt1 and sEng in PE only.Our data suggest that alpha methyldopa may have a specific effect on placental and/or endothelial cell function in pre-eclampsia patients, altering angiogenic proteins

Khalil Asma

Muttukrishna Shanthi

Harrington Kevin

Jauniaux Eric

Public Library of Science (PLOS)

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy.In a study conducted at University College Hospital and the Homerton University Hospital in London, we recruited 51 women with PE, 29 with gestational hypertension (GH), and 80 matched normotensive controls. Eight (16%) of the women with PE had severe disease. Placental samples were obtained from a further 48 women (14 PE, 10 GH and 24 matched controls). Serum levels of angiogenic factors were measured before and 24-48 hours after commencing antihypertensive therapy with alpha methyldopa for clinical indications. The same parameters were measured in placental extracts. In both PE (P<0.0001) and GH (P<0.05), serum sFlt-1 was increased and PlGF reduced at all gestations (P<0.001) compared to controls. Serum sEng levels were also increased in PE. Placental concentration of sFlt-1 and sEng was significantly higher in women with PE compared to controls and women with GH (P<0.0001). The concentration of PlGF was significantly lower in the placental tissue of women with PE compared to GH (P = 0.008). Antihypertensive treatment was associated with a significant fall in serum and placental content of sFlt1 and sEng in PE only.Our data suggest that alpha methyldopa may have a specific effect on placental and/or endothelial cell function in pre-eclampsia patients, altering angiogenic proteins

Directory of Open Access Journals

Ahmed A

Circulating angiogenic factors and the risk of preeclampsia.

Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin.

Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.

Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia.

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.

Soluble endoglin contributes to the pathogenesis of preeclampsia.

Urinary placental growth factor and risk of preeclampsia.

file:///data/remote/core/dit/data/public_library_of_science/pdf/c37/ZnRwOi8vZnRwLm5jYmkubmxtLm5paC5nb3YvcHViL3BtYy9vYV9wYWNrYWdlL2Q0L2IzL1BNQzI0NDc4NzcudGFyLmd6.pdf

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

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UCL Discovery

Public Library of Science (PLOS)

Public Library of Science (PLOS)

Directory of Open Access Journals