Please use this identifier to cite or link to this item: https://doi.org/10.1007/s00395-012-0316-y
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dc.titleMapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat
dc.contributor.authorMancini M.
dc.contributor.authorPetretto E.
dc.contributor.authorKleinert C.
dc.contributor.authorScavone A.
dc.contributor.authorDe T.
dc.contributor.authorCook S.
dc.contributor.authorSilhavy J.
dc.contributor.authorZidek V.
dc.contributor.authorPravenec M.
dc.contributor.authorD'Amati G.
dc.contributor.authorCamici P.G.
dc.date.accessioned2018-12-19T07:21:59Z
dc.date.available2018-12-19T07:21:59Z
dc.date.issued2013
dc.identifier.citationMancini M., Petretto E., Kleinert C., Scavone A., De T., Cook S., Silhavy J., Zidek V., Pravenec M., D'Amati G., Camici P.G. (2013). Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat. Basic Research in Cardiology 108 (1) : 316. ScholarBank@NUS Repository. https://doi.org/10.1007/s00395-012-0316-y
dc.identifier.issn03008428
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/149987
dc.description.abstractThe mechanisms underlying coronary microvascular remodeling and dysfunction, which are critical determinants of abnormal myocardial blood flow regulation in human hypertension, are poorly understood. The spontaneously hypertensive rat (SHR) exhibits many features of human hypertensive cardiomyopathy. We demonstrate that remodeling of intramural coronary arterioles is apparent in the SHR already at 4 weeks of age, i.e. before the onset of systemic hypertension. To uncover possible genetic determinants of coronary microvascular remodeling, we carried out detailed histological and histomorphometric analysis of the heart and coronary vasculature in 30 weeks old SHR, age-matched Brown Norway (BN-Lx) parentals and BXH/HXB recombinant inbred (RI) strains. Using previously mapped expression quantitative trait loci (eQTLs), we carried out a genome-wide association analysis between genetic determinants of cardiac gene expression and histomorphometric traits. This identified 36 robustly mapped eQTLs in the heart which were associated with medial area of intramural coronary arterioles [false discovery rate (FDR) ~5 %]. Transcripts, which were both under cis-acting genetic regulation and significantly correlated with medial area (FDR <5 %), but not with blood pressure indices, were prioritized and four candidate genes were identified (Rtel1, Pla2g5, Dnaja4 and Rcn2) according to their expression levels and biological functions. Our results demonstrate that genetic factors play a role in the development of coronary microvascular remodeling and suggest blood pressure independent candidate genes for further functional experiments. � 2012 Springer-Verlag Berlin Heidelberg.
dc.publisherSpringer Verlag
dc.sourceScopus
dc.subjectArterial hypertension
dc.subjectCandidate genes
dc.subjectCoronary circulation
dc.subjectMyocardial ischemia
dc.subjectRecombinant inbred strains
dc.subjectSpontaneously hypertensive rat
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1007/s00395-012-0316-y
dc.description.sourcetitleBasic Research in Cardiology
dc.description.volume108
dc.description.issue1
dc.description.page316
dc.published.statepublished
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