Human cardiac fibroblasts express an angiotensin receptor with unusual binding characteristics which is coupled to cellular proliferation.
To assess the cellular localization of angiotensin receptors in human heart, we isolated human cardiac fibroblasts from explanted end-stage failing human hearts. As judged by an immunofluorescence assay, the isolated cells consisted of 96% of fibroblasts. Using receptor binding studies, we could identify a single angiotensin binding site on these cells, with a Kd of 0.6nM and a Bmax of 1.5 fmol/mg protein. Inhibiting concentrations 50 for Ang II and Ang I/II (1-7) were 40nM and 10nM, respectively. Stimulation with Ang II (100 nM) and Ang I/II (1-7) (100nM) led to cellular proliferation which could not be inhibited by Losartan or PD 123319. These results suggest that human cardiac fibroblasts express an as yet unknown angiotensin receptor-subtype.
German Heart Institute, Berlin.
M
M
Neuss
V
V
Regitz-Zagrosek
A
A
Hildebrandt
E
E
Fleck
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D019808:Losartan; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D016895:Culture Media, Serum-Free; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan