title: Unloading the infarcted heart affect MMPs-TIMPs axis in a rat cardiac heterotopic transplantation model.
abstract: Ventricular assist devices may function as a bridge to recovery or heart transplantation, however, little is known about its mechanisms. This study examined the role of matrix metalloproteinases (MMP)-tissue inhibitors of metalloproteinases (TIMP) axis in the process of recovery after unloading in a rat ischemic-induce heart failure (HF) model. Myocardial infarction model was created with the coronary artery ligation. The infarcted rats hearts were unloaded by heterotopic cardiac transplantation (n=14). 2 weeks later, the function of normal and infarcted hearts with or without loading was evaluated by Langendorff perfusion model. The hearts were then harvested and prepared for the study of expression of MMPs and TIMPs. Developed pressure in the unloading group was higher than the loading group (P=0.0074). Unloading increased the ratio of TIMP-1-MMP-1(1.38±0.11 vs. 0.76±0.09, P<0.05), TIMP-2-MMP-2 (1.06±0.10 vs. 0.33±0.07, P<0.01), TIMP-3-MMP-9(1.07±0.08 vs. 0.59±0.06, P<0.05). Although MMP-1, 2, 9 were downregulated (P<0.01, 0.01, 0.05, respectively), TIMP-2 and TIMP-3 upregulated (P<0.01, 0.05, respectively), MMP-7 and TIMP-1 was not affected significantly. The infarcted cardiac function could be improved by unloading. It was attributed to downregulation of MMP-1, 2 and 9, and upregulation of TIMP-2 and -3, and furthermore, the ratio of TIMPs to MMPs was increased, which might be more sensitive than sole MMPs or TIMPs for the judgment of myocardial matrix homeostasis.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Wenzhou Medical College, Zhejiang, 325003, People's Republic of China.
authors.forename: Wei-jian
authors.initials: WJ
authors.lastname: Wang
authors.forename: Zi-li
authors.initials: ZL
authors.lastname: Meng
authors.forename: Yun-chang
authors.initials: YC
authors.lastname: Mo
authors.forename: Jun-wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Cheng-chao
authors.initials: CC
authors.lastname: Sun
authors.forename: Sheng-shou
authors.initials: SS
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D003331:Coronary Vessels / Q000601:surgery; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D006353:Heart-Assist Devices; D008026:Ligation; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000601:surgery*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D016042:Transplantation, Heterotopic / Q000502:physiology*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases