Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a n important role in several diseases. This study was undertaken to investig ate the mRNA synthesis of MMP2, MMP9, membrane-type 1 (MT1)-MMP, and matrix metalloproteinase inhibitors TIMP1 and T1MP2 by in situ hybridization in a set of heart mitral and aortic valves operatively removed due to degenerat ive or inflammatory valvular diseases, The material consisted of 21 valves, eight with endocarditis and 13 with a degenerative valvular disease, The s amples were studied by in situ hybridization with specific probes for MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2. Synthesis of MMP2 mRNA was found in seven valves, five with endocarditis and two with degenerative valvular disease. Signals for MMP9 mRNA were found in two cases with endocarditis and five c ases with degenerative valvular disease. No signal for MT1-MMP mRNA was fou nd in the lesions. TIMP1 mRNA, on the other hand, was found in 17 cases, bo th endocarditis and degenerative valvular disease. TIMP2 mRNA was found in three cases of endocarditis. The signals for MMP2, MMP9, TIMP1, and TIMP2 m RNA were localized in endothelial cells and in fibroblast-like cells expres sing a-smooth muscle actin, thus showing myofibroblast-type differentiation . The results show that matrix metalloproteinases MMP2 and MMP9, and matrix metalloproteinase inhibitors TIMP1 and TIMP2 mRNAs are synthesized in dise ased valves and suggest that they may contribute to matrix remodelling in v alvular disease. Copyright (C) 2001 John Wiley & Sons, Ltd.