title: Differential response of human cardiac fibroblasts to angiotensin I and angiotensin II.
abstract: The vasoactive peptide angiotensin II (Ang II) has been implicated as a mediator of myocardial fibrosis. We carried out a comparative investigation of the effects of Ang II and its precursor Ang I on collagen metabolism and proliferation in cultured human cardiac fibroblasts. Cardiac fibroblasts responded to both Ang I and Ang II with concentration-dependent increases in collagen synthesis but no proliferation. The stimulatory effect of Ang II was abolished by the AT(1) receptor antagonist losartan but not the AT(2) receptor antagonist PD123319. The response to Ang I was not affected by either antagonist, nor by the angiotensin-converting enzyme (ACE) inhibitor captopril. In conclusion, Both Ang I and Ang II stimulate collagen synthesis of human cardiac fibroblasts, the effect of Ang II occurring via the AT(1) receptor whilst Ang I appears to exert a direct effect through non-Ang II-dependent mechanisms. These results suggest distinct roles for angiotensin peptides in the development of cardiac fibrosis.
authors.affiliation: Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College School of Medicine at Harefield Hospital, Middlesex, UK. sassan.hafizi@klkemi.mas.lu.se
authors.forename: Sassan
authors.initials: S
authors.lastname: Hafizi
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Chester
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism
chemical_list: D000804:Angiotensin II; D003094:Collagen; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan