Angiotensin II induced cardiac dysfunction on a chip

Renita E. Horton, Moran Yadid, Megan L. McCain, Sean P. Sheehy, Francesco S. Pasqualini, Sung Jin Park, Alexander Cho, Patrick Campbell, Kevin Kit Parker

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

In 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.

Original languageEnglish
Article numbere0146415
JournalPLoS ONE
Volume11
Issue number1
DOIs
StatePublished - Jan 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Horton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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