“…Studies on affected tissues have shown up-regulation of MMP-1 and MMP-9 as well as collagen III (25), serotonin receptor 2B (18), MMP-1, MMP-14, and tissue inhibitors of metalloproteinases (TIMPs) such as TIMP-2, TIMP-3, and TIMP-4 (2, 3). Studies of tissue from affected hearts have also shown down-regulation of gene expression in the course of mitral valve disease, namely down-regulation of the microfibrillar, glycoprotein, and noncollagen extracellular matrix genes, TGF-ßR2, TGF-ß R3, and connective tissue growth factor (25); several MMPs, including MMP-2 (2), MMP-1, and MMP-13 (4); and TGF-ß3, TßR-II, αSMA, and MMP-3 (16).…”