Show simple item record

dc.contributor.authorAbraham, George R
dc.contributor.authorMorrow, Andrew J
dc.contributor.authorOliveira, Joana
dc.contributor.authorWeir-McCall, Jonathan R
dc.contributor.authorDavenport, Emma E
dc.contributor.authorBerry, Colin
dc.contributor.authorDavenport, Anthony P
dc.contributor.authorHoole, Stephen P
dc.date.accessioned2022-02-02T00:31:23Z
dc.date.available2022-02-02T00:31:23Z
dc.date.issued2022-04
dc.identifier.issn2352-9067
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333540
dc.description.abstractINTRODUCTION: Microvascular angina is a common cause of ischemia with non-obstructive coronary arteries (INOCA) and limited therapeutic options are available to those affected. Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathophysiology of microvascular angina. A large randomised, double blinded, placebo controlled crossover trial, the PRecIsion medicine with ZibotEntan in microvascular angina (PRIZE) trial is currently underway, investigating an endothelin receptor antagonist - Zibotentan, as a new drug treatment for microvascular angina. The trial uses a 'precision medicine' approach by preferential selection of those with higher ET-1 expression conferred by the PHACTR1 minor G allele single nucleotide polymorphism (SNP). The incidence of this SNP occurs in approximately one third of the population therefore a considerable number of screened patients will be ineligible for randomisation and the treatment phase of the trial. METHODS: In the PRIZE Endothelin (ET) Sub-Study, patients screened out of the PRIZE trial will be genotyped for other genetic variants in the ET-1 pathway. These will be correlated with phenotypic characteristics including exercise tolerance, angina severity and quantitative measures of microvascular function on cardiovascular MRI as well as mechanistic data on endothelin pathway signalling. CONCLUSIONS: The study will provide a comprehensive genotype and phenotype bio-resource identifying novel ET-1 genotypes to inform the potential wider use of endothelin receptor antagonists for this indication.
dc.description.sponsorshipWellcome Trust [WT107715/Z/15/Z, APD], British Heart Foundation [CB, RE/18/6134217], Medical Research Council [CB, MR/S018905/1], ].Jon Moulton Charity Trust [GRA, SPH]
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleMechanistic study of the effect of Endothelin SNPs in microvascular angina - Protocol of the PRIZE Endothelin Sub-Study.
dc.typeArticle
dc.publisher.departmentDepartment of Medicine
dc.date.updated2022-02-01T14:21:36Z
prism.publicationNameInt J Cardiol Heart Vasc
dc.identifier.doi10.17863/CAM.80960
dcterms.dateAccepted2022-02-20
rioxxterms.versionofrecord10.1016/j.ijcha.2022.100980
rioxxterms.versionVoR
dc.contributor.orcidWeir-McCall, Jonathan [0000-0001-5842-842X]
dc.contributor.orcidDavenport, Anthony [0000-0002-2096-3117]
dc.identifier.eissn2352-9067
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (107715/Z/15/Z)
pubs.funder-project-idMRC (via University of Glasgow) (303684)
cam.issuedOnline2022-02-25
cam.orpheus.counter1
cam.depositDate2022-02-01
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International