Cell Biochemistry and Biophysics

, Volume 44, Issue 1, pp 65–71 | Cite as

Peroxisome proliferator-activated receptor-γ ligands attenuate brain natriuretic peptide production and affect remodeling in cardiac fibroblasts in reoxygenation after hypoxia

  • Naoki Makino
  • Masahiro Sugano
  • Shinji Satoh
  • Junichi Oyama
  • Toyoki Maeda
Original article


Cardiac fibroblasts (CFs) participate in cardiac remodeling after hypoxic cardiac damage, and remodeling is thought to be mediated by CF synthesis of brain natriuretic peptide (BNP). It is unknown whether the peroxisome proliferator-activated receptors (PPARs), which mediate cellular signaling for growth and migration, affect BNP synthesis and whether PPARs participate in regulation of extracellular matrix protein (ECM) expression for remodeling. We examined the production of BNP in cultured neonatal ventricular CFs and its signaling system on collagen synthesis and on activation of matrix metalloproteinases (MMPs) in reoxygenation after hypoxia. BNP mRNA was detected in CFs, and a specific BNP protein, BNP1-32, was secreted into the media. Abundance of collagen I and III was increased in the media at reoxygenation. mRNA and protein levels for MMP-2 and the tissue inhibitor of metalloproteinase (TIMP)-1 were enhanced in CFs at reoxygenation. These observations also were noted in CFs after incubation with angiotensin II (10 μM) for 24 h. Pretreatment with pioglitaozone (0.1–10 μM) attenuated BNP mRNA and protein abundance of collagen III, MMP-2, and TIMP-1 in CFs at reoxygenation. The secreted BNP was also decreased by pioglitaozone in the media. Furthermore, PPAR activators inhibited reoxygenation-induced activation of nuclear factor (NF)-kB. These results demonstrate that PPAR activators inhibit BNP synthesis in CFs and imply that PPAR activators may regulate ECM remodeling partially through the NF-kB-mediated pathway.

Index Entries

Peroxisome proliferator-activated receptor activator brain natriuretic peptide heart hypertrophy matrix metalloproteinase 


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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Naoki Makino
    • 1
  • Masahiro Sugano
    • 1
  • Shinji Satoh
    • 1
  • Junichi Oyama
    • 1
  • Toyoki Maeda
    • 1
  1. 1.Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of BioregulationKyushu UniversityBeppuJapan

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