title: Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and transforming growth factor-β (TGF-β) in advanced canine myxomatous mitral valve disease.
abstract: This study investigated mitral valve and myocardial protein and gene expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and transforming growth factor-β (TGF-β) and plasma MMP and TGF-β concentrations in age-matched dog groups euthanized due to either advanced myxomatous mitral valve disease (MMVD) or other reasons. Furthermore, echocardiographic data and lumen/area ratio were correlated with tissue and plasma levels of MMPs, TIMPs and TGF-βs. Mitral valve and myocardial gene expression of MMP2, MMP14, TGF-β1 and TGF-β2 were increased and plasma MMP9 was decreased in advanced MMVD dogs. Myocardial gene expression of TIMP2 and TIMP3 were increased in advanced MMVD. All affected markers correlated to echocardiographic parameters. Significantly narrowed lumen/area ratio was associated with increased myocardial expression of MMP2, MMP14, TIMP2 and TIMP3. No differences in tissue protein expression were recorded. MMP2, MMP14, TIMP2, TIMP3, TGF-β1 and TGF-β2 appear to play a local role in the development of advanced MMVD.
authors.affiliation: Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: S G
authors.initials: SG
authors.lastname: Moesgaard
authors.affiliation: Laboklin GmbH, Bad Kissingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Aupperle
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Finland.
authors.forename: M M
authors.initials: MM
authors.lastname: Rajamäki
authors.affiliation: Din Veterinaer, Helsingborg, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Falk
authors.affiliation: Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: C E
authors.initials: CE
authors.lastname: Rasmussen
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: N E
authors.initials: NE
authors.lastname: Zois
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: lisbeth.hoier@sund.ku.dk.
authors.forename: L H
authors.initials: LH
authors.lastname: Olsen
mesh_terms: D000818:Animals; D001391:Azo Compounds; D017931:DNA Primers / Q000235:genetics; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D004452:Echocardiography / Q000662:veterinary; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry / Q000662:veterinary; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008945:Mitral Valve Prolapse / Q000378:metabolism / Q000662:veterinary*; D009206:Myocardium / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D018709:Statistics, Nonparametric; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D001391:Azo Compounds; D017931:DNA Primers; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; C009798:C.I. direct red 80; D020782:Matrix Metalloproteinases
keywords: Biomarker; Dog; Histopathology; Mitral valve; Myocardium