Simvastatin reduces TGF-β1-induced SMAD2/3-dependent human ventricular fibroblasts differentiation: Role of protein phosphatase activation.

ABSTRACT:

Background

Excessive cardiac fibrosis due to maladaptive remodeling leads to progression of cardiac dysfunction and is modulated by TGF-β1-activated intracellular phospho-SMAD signaling effectors and transcription regulators. SMAD2/3 phosphorylation, regulated by protein-phosphatases, has been studied in different cell types, but its role in human ventricular fibroblasts (hVFs) is not defined as a target to reduce cytokine-mediated excessive fibrotic response and adverse cardiac remodeling. Statins are a class of drugs reported to reduce cardiac fibrosis, although underlying mechanisms are not completely understood. We aimed to assess whether simvastatin-mediated reduction in TGF-β1-augmented profibrotic response involves reduction in phospho-SMAD2/3 owing to activation of protein-

SUBMITTER: Rizvi F 

PROVIDER: S-EPMC6146406 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature