An immunohistochemical study of the role of matrix metalloproteinases and their tissue inhibitors in chronic mitral valvular disease (valvular endocardiosis) in dogs

• Published in: The veterinary journal (1997) 2009-04, Vol.180 (1), p.88-94
• Main Authors: Aupperle, Heike, Thielebein, Jens, Kiefer, Birgit, März, Imke, Dinges, Gregor, Schoon, H.-A.
• Format: Article
• Language: English
• Subjects: animal proteins; Animals; Chronic valvular disease; Dog; dog diseases; Dog Diseases - enzymology; Dog Diseases - pathology; Dogs; enzyme inhibitors; extracellular matrix; Female; heart diseases; Heart Valve Diseases - enzymology; Heart Valve Diseases - pathology; Heart Valve Diseases - veterinary; heart valves; Immunohistochemistry; Immunohistochemistry - veterinary; Male; Matrix metalloproteinase; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Matrix Metalloproteinases - physiology; metalloproteinases; Mitral Valve; mitral valves; protein metabolism; protein synthesis; Severity of Illness Index; Tissue inhibitor of metalloproteinase; Tissue Inhibitor of Metalloproteinases - metabolism; Tissue Inhibitor of Metalloproteinases - physiology; Valvular endocardiosis
• ISSN: 1090-0233; 1532-2971
• DOI: 10.1016/j.tvjl.2007.11.011

While the pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, alterations in the activity of specific metalloproteinase enzymes and their inhibitors within the valve stroma are suspected of having a role. This study describes the immunohistochemical distribution pattern of matrix metalloproteinase (MMP) types 2, 9 and 14 and their tissue inhibitors, termed tissue inhibitors of metalloproteinase (TIMP), types 2 and 3, in normal canine mitral valves (MVs) ( n = 10) and in dogs with mild ( n = 7), moderate ( n = 14) and severe ( n = 9) CVD. In normal MVs, MMP-2 and -14, and TIMP-2 were expressed in isolated stromal cells. Tissue inhibitor of metalloproteinase-3 exhibited moderate intracellular and mild extracellular expression. With increasing severity of CVD, the expression of MMP-2 decreased. The number of stromal cells expressing MMP-14 increased, predominantly in the margins of the nodular lesions. Tissue inhibitor of metalloproteinase-2 and -3 expression increased both intra- and extracellularly. Matrix metalloproteinase-9 was not detected in normal or diseased valves. In conclusion, CVD was characterised by alterations in the distribution and intensity of valvular MMP and TIMP expression, suggesting that depressed catabolism and the accumulation of extracellular matrix components within affected valves contributes to their structural alteration and consequent loss of function.