Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload.

ABSTRACT: The cardiac pathological response to sustained pressure overload involves myocyte hypertrophy and dysfunction along with interstitial changes such as fibrosis and reduced capillary density. These changes are orchestrated by mechanical forces and factors secreted between cells. One such secreted factor is TGF-β, which is generated by and interacts with multiple cell types. Here we have shown that TGF-β suppression in cardiomyocytes was required to protect against maladaptive remodeling and involved noncanonical (non-Smad-related) signaling. Mouse hearts subjected to pressure overload and treated with a TGF-β-neutralizing Ab had suppressed Smad activation in the interstitium but not in myocytes, and noncanonical (TGF-β-activated kinase 1 [TAK1]) activation remained. Although fibrosis was gre

SUBMITTER: Koitabashi N 

PROVIDER: S-EPMC3104748 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature