Collagen production in cardiac fibroblasts during inhibition of angiotensin-converting enzyme and aminopeptidases.

Full Abstract

OBJECTIVE: To determine whether lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and bestatin, an aminopeptidase inhibitor with broad specificity, could affect collagen production in control and transforming growth factor (TGF)-beta1-treated cardiac fibroblasts. DESIGN AND METHODS: Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency, incubated with or without 600 pmol/l TGF-beta1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with the test products (lisinopril or bestatin) for 1 day in this medium with added ascorbic acid, beta-aminoproprionitrile and tritiated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. ACE activity was measured fluorimetrically with hippuryl-histidyl-leucine as substrate, and DNA with the bisbenzimide dye, Hoechst 33,258. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine-p-nitroanilide. RESULTS: Lisinopril dose-dependently reduced ACE activity in control and TGF-beta1-treated cardiac fibroblasts. Bestatin inhibited the basal and TGF-beta1-stimulated aminopeptidase activity in a concentration-dependent manner. Lisinopril (10 micromol/l) decreased (P < 0.05) the production of soluble and non-soluble collagen in control cardiac fibroblasts. TGF-beta1 (600 pmol/l) increased (P < 0.05) the production of soluble and non-soluble collagen, and this effect was decreased (P < 0.05) by lisinopril. Bestatin (100 micromol/l) reduced (P < 0.01) the production of soluble collagen in control and TGF-beta1-treated cardiac fibroblasts, but did not affect the production of non-soluble collagen in these cells. CONCLUSIONS: Our data suggest that ACE and aminopeptidases are involved in the basal and TGF-beta1-stimulated production of collagen in adult rat cardiac fibroblasts in culture.

Author information

Author/s: Lijnen, Paul J (PJ); Petrov, Victor V (VV); Fagard, Robert H (RH);

Affiliation: Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Catholic University of Leuven (K.U. Leuven), Belgium. paul.lijnen(-atsign-)med.kuleuven.ac.be

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of hypertension (J Hypertens), published in England. (Language: eng)

Reference: 2004-Jan; vol 22 (issue 1) : pp 209-16

Dates: Created 2004/04/26; Completed 2004/11/06; Revised 2006/11/15;

PMID: 15106813, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: J Hypertens. 2004 Jan;22(1):47-50. (PMID: 15106793)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Aminopeptidases - administration & dosage; antagonists & inhibitors; metabolism
Angiotensin-Converting Enzyme Inhibitors - administration & dosage
Aniline Compounds - metabolism
Animals
Cells, Cultured
Collagen - drug effects; metabolism
Dose-Response Relationship, Drug
Fibroblasts - drug effects; metabolism
Leucine - administration & dosage; analogs & derivatives
Lisinopril - administration & dosage
Male

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Angiotensin-Converting Enzyme Inhibitors (0) ; Aniline Compounds (0) ; Oligopeptides (0) ; Protease Inhibitors (0) ; Tgfb1 protein, rat (0) ; Transforming Growth Factor beta (0) ; Transforming Growth Factor beta1 (0) ; alanine-4-nitroanilide (1668-13-9) ; hippuryl-histidyl-leucine (31373-65-6) ; bestatin (58970-76-6) ; Leucine (61-90-5) ; Lisinopril (83915-83-7) ; Collagen (9007-34-5) ; Aminopeptidases (EC 3.4.11.-) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)

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