Endothelin-1 is an essential co-factor for beta2-adrenergic receptor-induced proliferation of human cardiac fibroblasts.
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.
Turner
Neil A
NA
Institute for Cardiovascular Research, Worsley Building, University of Leeds, Leeds LS2 9JT, UK. cvsnat@leeds.ac.uk
O'regan
David J
DJ
Ball
Stephen G
SG
Porter
Karen E
KE
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000319:Adrenergic beta-Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D011493:Protein Kinase C