title: 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.affiliation: Department of Pediatric Cardiology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan Shandong, 250021, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000818:Animals; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010455:Peptides; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling
chemical_list: D024042:Collagen Type I; D004396:Coloring Agents; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D002216:Captopril; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse