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Unloading the infarcted heart affect MMPs–TIMPs axis in a rat cardiac heterotopic transplantation model

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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.

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Acknowledgments

This research was supported by Grants from the Fok Ying Tung Education Foundation (121041) and National Natural Science Foundation of China (81070099).

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Authors and Affiliations

  1. Department of Anesthesiology, First Affiliated Hospital of Wenzhou Medical College, Zhejiang, 325003, People’s Republic of China

    Wei-jian Wang, Yun-chang Mo & Jun-wei Liu

  2. Department of Surgery and Research Center for Cardiac Regenerative Medicine, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, 10037, China

    Wei-jian Wang, Zi-li Meng, Sheng-shou Hu & Hao Zhang

  3. Department of Cardiovascular Surgery, Hebei Chest Hospital, Shijiazhuang, Hebei Province, 050041, China

    Zi-li Meng

  4. Department of Cardiac-Thoracic Surgery, First Affiliated Hospital of Wenzhou Medical College, Zhejiang, 325003, China

    Cheng-chao Sun

  5. Research Center for Cardiovascular Regenerative Medicine, Department of Cardiovascular Surgery, Cardiovascular Institute and Fuwai Hospital, A 167 Beilishilu, West District, Beijing, 100037, People’s Republic of China

    Hao Zhang

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  1. Wei-jian Wang
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Correspondence to Hao Zhang.

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Wei-jian Wang and Zi-li Meng contributed equally to this work.

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Wang, Wj., Meng, Zl., Mo, Yc. et al. Unloading the infarcted heart affect MMPs–TIMPs axis in a rat cardiac heterotopic transplantation model. Mol Biol Rep 39, 277–283 (2012). https://doi.org/10.1007/s11033-011-0736-z

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  • DOI: https://doi.org/10.1007/s11033-011-0736-z

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