title: Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-β mediated fibrosis.
abstract: BACKGROUND
  Mechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts' response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.
  
  
  RESULTS
  The effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.
  
  
  CONCLUSIONS
  We postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: Chris J
authors: CJ
authors: Watson
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: Dermot
authors: D
authors: Phelan
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: Maojia
authors: M
authors: Xu
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: Patrick
authors: P
authors: Collier
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: Roisin
authors: R
authors: Neary
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: Albert
authors: A
authors: Smolenski
authors: Heart Failure Unit, St Vincent's University Hospital Healthcare Group, Elm Park, Dublin, Ireland.
authors: Mark
authors: M
authors: Ledwidge
authors: Heart Failure Unit, St Vincent's University Hospital Healthcare Group, Elm Park, Dublin, Ireland.
authors: Kenneth
authors: K
authors: McDonald
authors: School of Medicine & Medical Science, The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors: John
authors: J
authors: Baugh