| Research Abstract |
The development of congestive heart failure is associated with left ventricular dilation and myocardial remodeling. The matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) activities play a significant role for remodeling of heart. Cardiac fibroblasts (CFs) as well as myocytes produce extracellular matrix proteins and participate in the remodeling of the heart. The brain natriuretic peptide (BNP) is well known as one of markers in heart failure of experimental and clinical situations. It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix production. In this study, we examined the production of BNP in neonatal cardiac CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs). BNP mRNA was detected in CFs, and a ELISA assay demonstrated that BNP was secreted into the media and the amount of BNP secretion was significantly augmented by tumor necrosis factor or angiotensin. When CFs was induced at reoxygenation after hypoxia for 24 hour, BNP mRNA expression was observed significantly and inhibited by the pretreatment with PPAR-r agonist (Pioglitazobe). In addition, protein expression of MMP-1, -2, and TLMP-1 was significantly increased in reoxygenation at 3 hours. PPAR-r agonist decreased the levels of expression of collageni, collagen ill, MMP-l, -2, and TIMP-l. In summary, this study reports that BNP is present in cultured CFs and that BNP levels increased at reoxygenation-induced damage of CFs. However, PPAR-r agonist may regulate collagen synthesis and alter MMPs protein levels. These in vitro findings support, a role for BNP as a regulator of myocardial structure via control of cardiac fibroblast function.
|
