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Impact of sex and pathophysiology on optimal drug choice in hypertensive rats: Quantitative insights for precision medicine

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dc.contributor.authorAhmed, Sameed
dc.contributor.authorSullivan, Jennifer C.
dc.contributor.authorLayton, Anita T.
dc.date.accessioned2022-01-28T21:00:41Z
dc.date.available2022-01-28T21:00:41Z
dc.date.issued2021-04
dc.description.abstractLess than half of all hypertensive patients receiving treatment are successful in normalizing their blood pressure. Despite the complexity and heterogeneity of hypertension, the current antihypertensive guidelines are not tailored to the individual patient. As a step toward individualized treatment, we develop a quantitative systems pharmacology model of blood pressure regulation in the spontaneously hypertensive rat (SHR) and generate sex-specific virtual populations of SHRs to account for the heterogeneity between the sexes and within the pathophysiology of hypertension. We then used the mechanistic model integrated with machine learning tools to study how variability in these mechanisms leads to differential responses in rodents to the four primary classes of antihypertensive drugs. We found that both the sex and the pathophysiological profile of the individual play a major role in the response to hypertensive treatments. These results provide insight into potential areas to apply precision medicine in human primary hypertension.en
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada || Canada 150 Research Chair programen
dc.identifier.urihttps://doi.org/10.1016/j.isci.2021.102341
dc.identifier.urihttp://hdl.handle.net/10012/18012
dc.language.isoenen
dc.publisherElsevieren
dc.relation.ispartofseriesiScience;
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectin silico biologyen
dc.subjectmedicineen
dc.subjectprecision medicineen
dc.subjectphysiologyen
dc.titleImpact of sex and pathophysiology on optimal drug choice in hypertensive rats: Quantitative insights for precision medicineen
dc.typeArticleen
dcterms.bibliographicCitationAhmed, S., Sullivan, J. C., & Layton, A. T. (2021). Impact of sex and pathophysiology on optimal drug choice in hypertensive rats: Quantitative insights for precision medicine. IScience, 24(4), 102341. https://doi.org/10.1016/j.isci.2021.102341en
uws.contributor.affiliation1Faculty of Scienceen
uws.contributor.affiliation1Faculty of Mathematicsen
uws.contributor.affiliation2Applied Mathematicsen
uws.contributor.affiliation2Biologyen
uws.contributor.affiliation2School of Pharmacyen
uws.contributor.affiliation2David R. Cheriton School of Computer Scienceen
uws.peerReviewStatusRevieweden
uws.scholarLevelFacultyen
uws.typeOfResourceTexten

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