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Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular diseas...

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Autores principales: Veiga-Lopez, Almudena, Sethuraman, Visalakshi, Navasiolava, Nastassia, Makela, Barbara, Olomu, Isoken, Long, Robert, van de Wetering, Koen, Martin, Ludovic, Aranyi, Tamas, Szeri, Flora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755719/
https://www.ncbi.nlm.nih.gov/pubmed/33363139
http://dx.doi.org/10.3389/fcell.2020.573727
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author Veiga-Lopez, Almudena
Sethuraman, Visalakshi
Navasiolava, Nastassia
Makela, Barbara
Olomu, Isoken
Long, Robert
van de Wetering, Koen
Martin, Ludovic
Aranyi, Tamas
Szeri, Flora
author_facet Veiga-Lopez, Almudena
Sethuraman, Visalakshi
Navasiolava, Nastassia
Makela, Barbara
Olomu, Isoken
Long, Robert
van de Wetering, Koen
Martin, Ludovic
Aranyi, Tamas
Szeri, Flora
author_sort Veiga-Lopez, Almudena
collection PubMed
description Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women.
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spelling pubmed-77557192020-12-24 Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk Veiga-Lopez, Almudena Sethuraman, Visalakshi Navasiolava, Nastassia Makela, Barbara Olomu, Isoken Long, Robert van de Wetering, Koen Martin, Ludovic Aranyi, Tamas Szeri, Flora Front Cell Dev Biol Cell and Developmental Biology Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women. Frontiers Media S.A. 2020-12-09 /pmc/articles/PMC7755719/ /pubmed/33363139 http://dx.doi.org/10.3389/fcell.2020.573727 Text en Copyright © 2020 Veiga-Lopez, Sethuraman, Navasiolava, Makela, Olomu, Long, van de Wetering, Martin, Aranyi and Szeri. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Veiga-Lopez, Almudena
Sethuraman, Visalakshi
Navasiolava, Nastassia
Makela, Barbara
Olomu, Isoken
Long, Robert
van de Wetering, Koen
Martin, Ludovic
Aranyi, Tamas
Szeri, Flora
Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
title Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
title_full Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
title_fullStr Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
title_full_unstemmed Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
title_short Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk
title_sort plasma inorganic pyrophosphate deficiency links multiparity to cardiovascular disease risk
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755719/
https://www.ncbi.nlm.nih.gov/pubmed/33363139
http://dx.doi.org/10.3389/fcell.2020.573727
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