Mechanical overload in the heart induces pathological remodeling that typcially leads to heart failure. We sought to build an in vitro model of heart failure by applying cyclic stretch to engineered isotropic (iso) and anisotropic (aniso) NRVM tissues. We used micoarrays to determine the effects of longitudinal and transvserse cyclic stretch on gene expression in engineered NRVM cardiac tissues. We found that cyclic stretch induced up-regulation of several known indicators of heart faliure, independent of the direction of stretch.
Overall design
NRVMs were seeded on silicone membranes coated with isotropic (iso) fibronectin (FN) or micropatterned with FN (aniso), cultured statically for 1h (t=0h), and stretched for increasing amount of time (t=6h, 24h, 96h) before RNA extraction and hybridization on Affymetrix microarrays. For aniso tissues, stretch was applied in either the longitudinal (long) or transverse (trans) direction. RNA was collected over six primary NRVM harvests and thus RNA was also extracted and analyzed from samples seeded for 1h (at t=0h) on iso FN to be used to normalize across cell harvests.
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