title: Angiotensin II Induced Cardiac Dysfunction on a Chip.
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.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.|Department of Agriculture and Biological Engineering, James Worth Bagley College of Engineering, College of Agriculture and Life Sciences, Mississippi State University, Starkville, Mississippi, United States of America.
authors.forename: Renita E
authors.initials: RE
authors.lastname: Horton
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Moran
authors.initials: M
authors.lastname: Yadid
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Megan L
authors.initials: ML
authors.lastname: McCain
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sheehy
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Pasqualini
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Cho
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Campbell
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008962:Models, Theoretical; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000804:Angiotensin II