Endothelin-1 is an essential co-factor for beta2-adrenergic receptor-induced proliferation of human cardiac fibroblasts

FEBS Lett. 2004 Oct 8;576(1-2):156-60. doi: 10.1016/j.febslet.2004.08.080.

Abstract

We previously demonstrated that chronic stimulation of the beta2-adrenergic receptor (beta2-AR) increases proliferation of cultured human cardiac fibroblasts (CF) via an autocrine mechanism. Here, we investigated the role of endothelin-1 (ET-1) in this process. ETA-receptor antagonism or protein kinase C inhibition abolished the beta2-AR-induced increase in cell proliferation. RT-PCR and ELISA analysis demonstrated that although CF synthesized and secreted ET-1, this occurred independently of beta2-AR stimulation. Furthermore, despite activation of the MAP kinase pathway, ET-1 treatment did not stimulate CF proliferation. Therefore, the role of ET-1 in this process is that of an essential co-factor acting independently of beta2-AR stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Cell Division / drug effects*
  • Cells, Cultured
  • Endothelin-1 / metabolism*
  • Endothelin-1 / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Humans
  • Kinetics
  • Models, Biological
  • Myocardium / cytology*
  • Protein Kinase C / antagonists & inhibitors
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Adrenergic beta-Antagonists
  • Endothelin-1
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • Protein Kinase C