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dc.contributor.authorHorton, Renita E.en_US
dc.contributor.authorYadid, Moranen_US
dc.contributor.authorMcCain, Megan L.en_US
dc.contributor.authorSheehy, Sean P.en_US
dc.contributor.authorPasqualini, Francesco S.en_US
dc.contributor.authorPark, Sung-Jinen_US
dc.contributor.authorCho, Alexanderen_US
dc.contributor.authorCampbell, Patricken_US
dc.contributor.authorParker, Kevin Kiten_US
dc.date.accessioned2016-03-01T19:50:46Z
dc.date.issued2016en_US
dc.identifier.citationHorton, Renita E., Moran Yadid, Megan L. McCain, Sean P. Sheehy, Francesco S. Pasqualini, Sung-Jin Park, Alexander Cho, Patrick Campbell, and Kevin Kit Parker. 2016. “Angiotensin II Induced Cardiac Dysfunction on a Chip.” PLoS ONE 11 (1): e0146415. doi:10.1371/journal.pone.0146415. http://dx.doi.org/10.1371/journal.pone.0146415.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:25658513
dc.description.abstractIn vitro disease models offer the ability to study specific systemic features in isolation to better understand underlying mechanisms that lead to dysfunction. Here, we present a cardiac dysfunction model using angiotensin II (ANG II) to elicit pathological responses in a heart-on-a-chip platform that recapitulates native laminar cardiac tissue structure. Our platform, composed of arrays of muscular thin films (MTF), allows for functional comparisons of healthy and diseased tissues by tracking film deflections resulting from contracting tissues. To test our model, we measured gene expression profiles, morphological remodeling, calcium transients, and contractile stress generation in response to ANG II exposure and compared against previous experimental and clinical results. We found that ANG II induced pathological gene expression profiles including over-expression of natriuretic peptide B, Rho GTPase 1, and T-type calcium channels. ANG II exposure also increased proarrhythmic early after depolarization events and significantly reduced peak systolic stresses. Although ANG II has been shown to induce structural remodeling, we control tissue architecture via microcontact printing, and show pathological genetic profiles and functional impairment precede significant morphological changes. We assert that our in vitro model is a useful tool for evaluating tissue health and can serve as a platform for studying disease mechanisms and identifying novel therapeutics.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0146415en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725954/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectGeneticsen
dc.subjectGene Expressionen
dc.subjectMedicine and Health Sciencesen
dc.subjectCardiologyen
dc.subjectHeart Failureen
dc.subjectEngineering and Technologyen
dc.subjectArchitectural Engineeringen
dc.subjectPhysical Sciencesen
dc.subjectMaterials Scienceen
dc.subjectMaterials by Structureen
dc.subjectThin Filmsen
dc.subjectBiophysicsen
dc.subjectIon Channelsen
dc.subjectCalcium Channelsen
dc.subjectPhysicsen
dc.subjectPhysiologyen
dc.subjectElectrophysiologyen
dc.subjectNeurophysiologyen
dc.subjectNeuroscienceen
dc.subjectBiochemistryen
dc.subjectProteinsen
dc.subjectBiotechnologyen
dc.subjectGenetic Engineeringen
dc.subjectArrhythmiaen
dc.subjectMembrane Potentialen
dc.subjectDepolarizationen
dc.titleAngiotensin II Induced Cardiac Dysfunction on a Chipen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorHorton, Renita E.en_US
dc.date.available2016-03-01T19:50:46Z
dc.identifier.doi10.1371/journal.pone.0146415*
dash.contributor.affiliatedCampbell, Patrick
dash.contributor.affiliatedHorton, Renita E.
dash.contributor.affiliatedSheehy, Sean Paul
dash.contributor.affiliatedParker, Kevin
dash.contributor.affiliatedPasqualini, Francesco


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