Decreased Substrate Stiffness Promotes a Hypofibrotic Phenotype in Cardiac Fibroblasts.

ABSTRACT: A hypofibrotic phenotype has been observed in cardiac fibroblasts (CFs) isolated from a volume overload heart failure model, aortocaval fistula (ACF). This paradoxical phenotype results in decreased ECM synthesis despite increased TGF-β presence. Since ACF results in decreased tissue stiffness relative to control (sham) hearts, this study investigates whether the effects of substrate stiffness could account for the observed hypofibrotic phenotype in CFs isolated from ACF. CFs isolated from ACF and sham hearts were plated on polyacrylamide gels of a range of stiffness (2 kPa to 50 kPa). Markers related to cytoskeletal and fibrotic proteins were measured. Aspects of the hypofibrotic phenotype observed in ACF CFs were recapitulated by sham CFs on soft substrates. For instance, sham CFs on the

SUBMITTER: Childers RC 

PROVIDER: S-EPMC8230133 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature