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Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries

Hypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension....

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Autores principales: Little, Robert, Zi, Min, Hammad, Sally K., Nguyen, Loan, Njegic, Alexandra, Kurusamy, Sathishkumar, Prehar, Sukhpal, Armesilla, Angel L., Neyses, Ludwig, Austin, Clare, Cartwright, Elizabeth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595685/
https://www.ncbi.nlm.nih.gov/pubmed/28795531
http://dx.doi.org/10.1111/acel.12637
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author Little, Robert
Zi, Min
Hammad, Sally K.
Nguyen, Loan
Njegic, Alexandra
Kurusamy, Sathishkumar
Prehar, Sukhpal
Armesilla, Angel L.
Neyses, Ludwig
Austin, Clare
Cartwright, Elizabeth J.
author_facet Little, Robert
Zi, Min
Hammad, Sally K.
Nguyen, Loan
Njegic, Alexandra
Kurusamy, Sathishkumar
Prehar, Sukhpal
Armesilla, Angel L.
Neyses, Ludwig
Austin, Clare
Cartwright, Elizabeth J.
author_sort Little, Robert
collection PubMed
description Hypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension. Here, we present the effects of reduction in the expression of PMCA1 on BP and small artery structure and function when combined with advancing age. Heterozygous PMCA1 null mice (PMCA1(Ht)) were generated and conscious BP was measured at 6 to 18 months of age. Passive and active properties of isolated small mesenteric arteries were examined by pressure myography. PMCA1(Ht) mice exhibited normal BP at 6 and 9 months of age but developed significantly elevated BP when compared to age‐matched wild‐type controls at ≥12 months of age. Decreased lumen diameter, increased wall thickness and increased wall:lumen ratio were observed in small mesenteric arteries from animals 9 months of age and older, indicative of eutrophic remodelling. Increases in mesenteric artery intrinsic tone and global intracellular calcium were evident in animals at both 6 and 18 months of age. Thus, decreased expression of PMCA1 is associated with increased BP when combined with advancing age. Changes in arterial structure precede the elevation of BP. Pathways involving PMCA1 may be a novel target for BP regulation in the elderly.
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spelling pubmed-55956852017-10-01 Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries Little, Robert Zi, Min Hammad, Sally K. Nguyen, Loan Njegic, Alexandra Kurusamy, Sathishkumar Prehar, Sukhpal Armesilla, Angel L. Neyses, Ludwig Austin, Clare Cartwright, Elizabeth J. Aging Cell Original Articles Hypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension. Here, we present the effects of reduction in the expression of PMCA1 on BP and small artery structure and function when combined with advancing age. Heterozygous PMCA1 null mice (PMCA1(Ht)) were generated and conscious BP was measured at 6 to 18 months of age. Passive and active properties of isolated small mesenteric arteries were examined by pressure myography. PMCA1(Ht) mice exhibited normal BP at 6 and 9 months of age but developed significantly elevated BP when compared to age‐matched wild‐type controls at ≥12 months of age. Decreased lumen diameter, increased wall thickness and increased wall:lumen ratio were observed in small mesenteric arteries from animals 9 months of age and older, indicative of eutrophic remodelling. Increases in mesenteric artery intrinsic tone and global intracellular calcium were evident in animals at both 6 and 18 months of age. Thus, decreased expression of PMCA1 is associated with increased BP when combined with advancing age. Changes in arterial structure precede the elevation of BP. Pathways involving PMCA1 may be a novel target for BP regulation in the elderly. John Wiley and Sons Inc. 2017-08-09 2017-10 /pmc/articles/PMC5595685/ /pubmed/28795531 http://dx.doi.org/10.1111/acel.12637 Text en © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Little, Robert
Zi, Min
Hammad, Sally K.
Nguyen, Loan
Njegic, Alexandra
Kurusamy, Sathishkumar
Prehar, Sukhpal
Armesilla, Angel L.
Neyses, Ludwig
Austin, Clare
Cartwright, Elizabeth J.
Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
title Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
title_full Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
title_fullStr Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
title_full_unstemmed Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
title_short Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
title_sort reduced expression of pmca1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595685/
https://www.ncbi.nlm.nih.gov/pubmed/28795531
http://dx.doi.org/10.1111/acel.12637
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