Human cardiac fibroblasts express B-type natriuretic peptide: fluvastatin ameliorates its up-regulation by interleukin-1α, tumour necrosis factor-α and transforming growth factor-β

نویسندگان

  • Rudolf Jarai
  • Christoph Kaun
  • Thomas W Weiss
  • Walter S Speidl
  • Kathrin Rychli
  • Gerald Maurer
  • Kurt Huber
  • Johann Wojta
چکیده

B-type natriuretic peptide (BNP) is a cardiac hormone, which plays a major role in body fluid and cardiovascular homeostasis. Produced by cardiac ventricles, its expression is highly regulated by various mediators. Canine cardiac fibroblasts have been identified as a source of BNP. Cardiac fibroblasts are key regulators of myocardial structure and function. We treated cultured human adult cardiac fibroblasts (HACF) with 2000 U/ml tumour necrosis factor(TNF), 200 U/ml interleukin-1 (IL-1 ) or 50 ng/ml transforming growth factor(TGF) in the presence or absence of 500 nM fluvastatin. N-terminal pro-BNP (Nt-proBNP) concentration was determined by a competitive enzyme immunoassay. RealTime polymerase chain reaction (real-time PCR) was performed to investigate changes in BNP mRNA expression. Nt-proBNP peptide was present in the conditioned media of HACF and incubation with fluvastatin significantly reduced Nt-proBNP peptide levels. Treatment of HACF with TNF, IL-1 or TGFsignificantly increased Nt-proBNP levels compared with untreated cells. This effect was completely abolished in the presence of fluvastatin. Real-time PCR analysis confirmed these changes at the level of mRNA expression. Our data suggest that cardiac fibroblasts are a potential source of BNP in the human heart. Pro-inflammatory cytokines, associated with ventricular dysfunction and cardiac fibrosis, seem to be major inducers of BNP production in cardiac fibroblasts. This effect can be reverted by a statin. Based on our data, we speculate that elevated plasma BNP levels might not only reflect increased myocardial stretch but also inflammatory and remodelling processes. A possible benefit of statin-induced reduction in BNP production requires further studies.

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عنوان ژورنال:

دوره 13  شماره 

صفحات  -

تاریخ انتشار 2009