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Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?

Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the ‘two-stage model’ of pre-eclampsia in which abnormal spiral arteries modifica...

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Autores principales: Ahmed, Asif, Ramma, Wenda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354257/
https://www.ncbi.nlm.nih.gov/pubmed/25303561
http://dx.doi.org/10.1111/bph.12977
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author Ahmed, Asif
Ramma, Wenda
author_facet Ahmed, Asif
Ramma, Wenda
author_sort Ahmed, Asif
collection PubMed
description Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the ‘two-stage model’ of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the ‘accelerator’. The ‘braking system’ includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H(2)S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator–brake defect disorder. CO and H(2)S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line. LINKED ARTICLES: This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6
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spelling pubmed-43542572015-03-16 Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm? Ahmed, Asif Ramma, Wenda Br J Pharmacol Themed Section: Pharmacology of the Gasotransmitters Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the ‘two-stage model’ of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the ‘accelerator’. The ‘braking system’ includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H(2)S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator–brake defect disorder. CO and H(2)S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line. LINKED ARTICLES: This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 BlackWell Publishing Ltd 2015-03 2015-02-27 /pmc/articles/PMC4354257/ /pubmed/25303561 http://dx.doi.org/10.1111/bph.12977 Text en Copyright © 2015 The British Pharmacological Society http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Themed Section: Pharmacology of the Gasotransmitters
Ahmed, Asif
Ramma, Wenda
Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
title Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
title_full Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
title_fullStr Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
title_full_unstemmed Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
title_short Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
title_sort unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?
topic Themed Section: Pharmacology of the Gasotransmitters
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354257/
https://www.ncbi.nlm.nih.gov/pubmed/25303561
http://dx.doi.org/10.1111/bph.12977
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