ADAMTS-1 contributes to the antifibrotic effect of captopril by accelerating the degradation of type I collagen in chronic viral myocarditis.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors have been demonstrated to have antifibrotic activity in myocardial fibrosis. A distintegrin and metalloprotease with thrombospondin type 1 motifs (ADAMTS-1) is a newly discovered metalloproteinase. It was reported ADAMTS-1 had novel gelatin (type I collagen) degrading activities. We examined the role of ADAMTS-1 in the antifibrotic activity of the ACE inhibitor Captopril in a chronic viral myocarditis (CVMC) model. Balb/c mice were assigned to five groups: normal control group1 (group 1), normal control group2 (group 2), CVMC model group (group 3), CVMC control group (group 4) and Captopril therapy group (group 5). Group 3, 4 and 5 received Coxsackievirus B(3) to induce CVMC and group 5 was treated with Captopril (100mg/kg)for 28days. Heart sections were stained with picrosirius red and collagen volume fraction calculated. ADAMTS-1 expression was determined by Western blot. Type I collagen and carboxyterminal telopeptide of type I collagen (ICTP) were measured by RT-PCR. Group 4 mice had significantly increased collagen volume fraction compared to groups 2 and 5 (P<0.001, P<0.001, respectively) and higher type I collagen mRNA expression than groups 2 and 5 (P<0.001, P<0.001, respectively). Group 5 ADAMTS-1 and ICTP expression was significantly higher than in groups 2 and 4 (P<0.001, P<0.001, respectively). ADAMTS-1 levels in group 5 negatively correlated with collagen volume fraction (r=-0.68, P<0.01) and type I collagen (r=-0.67, P<0.01) but positively correlated with ICTP (r=0.72, P<0.01). We conclude that ADAMTS-1 contributes to the antifibrotic effect of Captopril by accelerating the degradation of type I collagen in CVMC.

• Authors: Chunyan Guo, Yi Wang, Hao Liang, Jie Zhang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 629 Issue 1-3 Pg. 104-10 (Mar 10 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20006601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier B.V. All rights reserved.

Chemical References

• Collagen Type I
• Coloring Agents
• Peptide Fragments
• Peptides
• Procollagen
• collagen type I trimeric cross-linked peptide
• Captopril
• ADAM Proteins
• ADAMTS1 Protein
• Adamts1 protein, mouse

Topics

• ADAM Proteins (metabolism)
• ADAMTS1 Protein
• Animals
• Blotting, Western
• Captopril (pharmacology, therapeutic use)
• Chronic Disease
• Collagen Type I (genetics, metabolism)
• Coloring Agents (metabolism)
• Fibrinolysis (drug effects)
• Fibrosis (drug therapy)
• Kinetics
• Male
• Mice
• Mice, Inbred BALB C
• Myocarditis (drug therapy, metabolism, pathology, virology)
• Peptide Fragments (genetics, metabolism)
• Peptides
• Procollagen (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Staining and Labeling