Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783626401143848960 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7755719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT veigalopezalmudena plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT sethuramanvisalakshi plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT navasiolavanastassia plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT makelabarbara plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT olomuisoken plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT longrobert plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT vandeweteringkoen plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT martinludovic plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT aranyitamas plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk AT szeriflora plasmainorganicpyrophosphatedeficiencylinksmultiparitytocardiovasculardiseaserisk |