Profibrotic effects of endothelin-1 via the ETA Receptor in cultured human cardiac fibroblasts

Sassan Hafizi, J. Wharton, A. Chester, M. Yacoub

Research output: Contribution to journalArticlepeer-review


Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [3H]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788. Results: ET-1 elicited a potent collagen synthesis response in cardiac fibroblasts, with a maximum 29±5% increase that was abolished by BQ123. Cardiac fibroblasts responded to ET-1 with a concentration-dependent decrease in DNA synthesis rate. The effects of ET-1 were similar to those of TGF-β. Radioligand binding studies revealed the presence of high-affinity ET-1 binding sites on these cells, which were upregulated by treatment with the growth factors PDGF and EGF but downregulated by TGF-β. Conclusions: These results therefore implicate ET-1 as a trophic agent in the human heart with the ability to influence the development of cardiac fibrosis.
Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalCellular Physiology and Biochemistry
Issue number4-6
Publication statusPublished - 2004


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