Reduced Expression of PMCA1 is Associated with Increased Blood Pressure with Age Which is Preceded by Remodeling of Resistance Arteries

2.50
Hdl Handle:
http://hdl.handle.net/2436/620527
Title:
Reduced Expression of PMCA1 is Associated with Increased Blood Pressure with Age Which is Preceded by Remodeling of Resistance Arteries
Authors:
Little, Robert; Zi, Min; Hammad, Sally K; Nguyen, Loan; Njegic, Alexandra; Kurusamy, Sathishkumar; Prehar, Sukhpal; Armesilla, Angel Luis; Neyses, Ludwig; Austin, Clare; Cartwright, Elizabeth J.
Abstract:
Hypertension is a well-established risk factor for adverse cardiovascular events and older age is a risk factor for the development of hypertension. Genome wide 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 (PMCA1Ht) 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. PMCA1Ht 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 was observed in small mesenteric arteries from animals 9 months of age and older, indicative of eutrophic remodeling. 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.
Publisher:
Wiley
Journal:
Aging cell
Issue Date:
Oct-2017
URI:
http://hdl.handle.net/2436/620527
Additional Links:
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1474-9726/issues
Type:
Article
Language:
en
ISSN:
1474-9718
Appears in Collections:
FSE

Full metadata record

DC FieldValue Language
dc.contributor.authorLittle, Roberten
dc.contributor.authorZi, Minen
dc.contributor.authorHammad, Sally Ken
dc.contributor.authorNguyen, Loanen
dc.contributor.authorNjegic, Alexandraen
dc.contributor.authorKurusamy, Sathishkumaren
dc.contributor.authorPrehar, Sukhpalen
dc.contributor.authorArmesilla, Angel Luisen
dc.contributor.authorNeyses, Ludwigen
dc.contributor.authorAustin, Clareen
dc.contributor.authorCartwright, Elizabeth J.en
dc.date.accessioned2017-06-23T08:59:44Z-
dc.date.available2017-06-23T08:59:44Z-
dc.date.issued2017-10-
dc.identifier.issn1474-9718en
dc.identifier.urihttp://hdl.handle.net/2436/620527-
dc.description.abstractHypertension is a well-established risk factor for adverse cardiovascular events and older age is a risk factor for the development of hypertension. Genome wide 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 (PMCA1Ht) 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. PMCA1Ht 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 was observed in small mesenteric arteries from animals 9 months of age and older, indicative of eutrophic remodeling. 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.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1474-9726/issuesen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectBlood pressureen
dc.subjecthypertensionen
dc.subjectPMCAen
dc.subjectATP2B1en
dc.subjectarterial remodelingen
dc.titleReduced Expression of PMCA1 is Associated with Increased Blood Pressure with Age Which is Preceded by Remodeling of Resistance Arteriesen
dc.typeArticleen
dc.identifier.journalAging cellen
dc.date.accepted2017-06-
rioxxterms.funderInternalen
rioxxterms.identifier.projectUoW230617AAen
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0en
rioxxterms.licenseref.startdate2017-10-01en
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