title: Immunohistochemical detection of differentially localized up-regulation of lysyl oxidase and down-regulation of matrix metalloproteinase-1 in rhesus monkey model of chronic myocardial infarction.
abstract: Myocardial remodeling after ischemic infarction is characterized by collagen accumulation leading to replacement and interstitial fibrosis. Type I and III collagens are predominant components in cardiac fibrosis. Lysyl oxidase (LOX) facilitates the cross-linking of type I and III fibrils, resulting in the formation of stiff fibers and their subsequent tissue deposition. However, the matrix metalloproteinases (MMPs), a family of zinc-dependent enzymes, function in the degradation of the collagen components of extracellular matrix. Tissue inhibitors for MMPs (TIMPs) manipulate the action of MMPs. To understand the contribution of these molecules to cardiac fibrosis, we developed a rhesus monkey model to determine the changes in LOX, MMP1 and TIMP1 in relation to collagen deposition after myocardial ischemic infarction. Male rhesus monkeys were subjected to left anterior descending artery ligation along with sham-operated controls. Histological examination and immunochemistry were performed eight weeks after the ischemic injury. The results showed that both type I and III collagens were increased in the scar area and in the interstitium, and the ratio of type I/III collagens also increased in the scar area but not in the interstitium. The expression of LOX was up-regulated, but the expression of MMP1 was down-regulated in residual myocytes of the scar area and the border zone. The expression of TIMP1 was not changed. The data thus demonstrated that the collagen deposition in infarcted myocardium is correlated with an enhanced cross-linking capacity and a decreased degradation process.
authors: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041,  China.
authors: Yuping
authors: Y
authors: Xie
authors: Jianmin
authors: J
authors: Chen
authors: Pengfei
authors: P
authors: Han
authors: Pingliang
authors: P
authors: Yang
authors: Jianglong
authors: J
authors: Hou
authors: Y James
authors: YJ
authors: Kang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D008249:Protein-Lysine 6-Oxidase; D020781:Matrix Metalloproteinase 1