Recapitulating maladaptive, multiscale remodeling of failing myocardium on a chip.

ABSTRACT: The lack of a robust pipeline of medical therapeutic agents for the treatment of heart disease may be partially attributed to the lack of in vitro models that recapitulate the essential structure-function relationships of healthy and diseased myocardium. We designed and built a system to mimic mechanical overload in vitro by applying cyclic stretch to engineered laminar ventricular tissue on a stretchable chip. To test our model, we quantified changes in gene expression, myocyte architecture, calcium handling, and contractile function and compared our results vs. several decades of animal studies and clinical observations. Cyclic stretch activated gene expression profiles characteristic of pathological remodeling, including decreased α- to β-myosin heavy chain ratios, and induced maladapti

SUBMITTER: McCain ML 

PROVIDER: S-EPMC3683774 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature