Title: Collagen production in cardiac fibroblasts during inhibition of aminopeptidase B
Authors: Lijnen, Paul ×
Petrov, Victor
Turner, Marisa
Fagard, Robert #
Issue Date: Sep-2005
Series Title: Journal of the renin-angiotensin-aldosterone system : JRAAS vol:6 issue:2 pages:69-77
Abstract: OBJECTIVE. To determine whether the aminopeptidase B inhibitor, arphamenine A, could affect collagen production and expression in control and TGF-ss1-treated cardiac fibroblasts. DESIGN AND METHODS. Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency and incubated with and without 600 pmol/l TGF-ss1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with 100 mol/l arphamenine A for 1 day in this medium with added ascorbic acid, ss-aminopropionitrile and titriated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Matrix metalloproteinase (MMP) and lysyl oxidase activity were assayed in the conditioned medium. A semi-quantitative reverse transcriptase- polymerase chain reaction was used to examine the expression of lysyl oxidase and collagen type I and III. RESULTS. Arphamenine A dose-dependently inhibited basal and TGF-ss1-stimulated aminopeptidase activity. Arphamenine A reduced soluble and non-soluble collagen production in control and TGF-ss1-treated cardiac fibroblasts, while it decreased collagen type I and III expression only in TGF-ss1-treated fibroblasts. Lysyl oxidase, MMP-1 and MMP-2 activity were inhibited by arphamenine A in the conditioned media of control and TGF-ss1-treated cardiac fibroblasts. CONCLUSIONS. Our data show that the specific aminopeptidase B inhibitor, arphamenine A, reduces collagen production in cardiac fibroblasts and that this reduction is accompanied by a pronounced inhibition of lysyl oxidase.
ISSN: 1470-3203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hypertension and Cardiovascular Epidemiology
× corresponding author
# (joint) last author

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