title: Dynamic expression profiles of MMPs/TIMPs and collagen deposition in mechanically unloaded rat heart: implications for left ventricular assist device support-induced cardiac alterations.
abstract: Left ventricular assist devices (LVADs) ameliorate heart failure by reducing preload and afterload. However, extracellular matrix (ECM) deposition after application of LVADs is not clearly defined. The purpose of the present study was to investigate ECM remodeling after mechanical unloading in a rat heart transplant model. Sixty male Lewis rats were subjected to abdominal heterotopic heart transplantation, and the transplanted hearts were pressure- and volume-unloaded. The age- and weight- matched male Lewis rats who had undergone open thoracic surgeries were used as the control. Left ventricle ECM accumulation and the expression/activity of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs) were measured on the third, seventh, and fourteenth days after transplantation/sham surgery. Compared with the control group, myocardial ECM deposition significantly increased on the seventh and fourteenth days after heart transplantation (P < 0.05) and peaked on the 14th day. The gelatinase activity as well as mRNA expression of MMP-2 and MMP-9 significantly increased after transplantation (P < 0.05). Both mRNA and protein levels of TIMP-1 and TIMP-2 significantly increased compared with those of the control group. Mechanical unloading may lead to adverse remodeling of the ECM of the left ventricle. The underlying mechanism may due to the imbalance of the MMP/TIMP system, especially the remarkable upregulation of TIMPs in the pressure and volume unloaded heart.
authors: Division of Cardiology, Shandong Corps Hospital of Chinese People's Armed Police Forces, Jinan, Shandong, People's Republic of China.
authors: Lu
authors: L
authors: Wang
authors: Yu-Xian
authors: YX
authors: Xu
authors: Xiao-Jie
authors: XJ
authors: Du
authors: Quan-Ge
authors: QG
authors: Sun
authors: Ying-Jun
authors: YJ
authors: Tian
mesh_terms: D000005:Abdomen; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006353:Heart-Assist Devices / Q000009:adverse effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D016042:Transplantation, Heterotopic; D020257:Ventricular Remodeling
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9