• Open Access

Type-specific dysregulation of matrix metalloproteinases and their tissue inhibitors in end-stage heart failure patients: relationship between MMP-10 and LV remodelling

Authors

  • Yingjie Wei,

    Corresponding author
    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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    • These authors contributed equally.

  • Chuanjue Cui,

    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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    • These authors contributed equally.

  • Mitja Lainscak,

    1. University Clinic of Respiration and Allergic Disease Golnik, Division of Cardiology, Golnik, Slovenia
    2. Applied Cachexia Research, Dept of Cardiology, Charité, Campus Virchow-Klinikum, Berlin, Germany
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    • These authors contributed equally.

  • Xiaoling Zhang,

    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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  • Jun Li,

    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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  • Jie Huang,

    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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  • Hao Zhang,

    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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  • Zhe Zheng,

    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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  • Shengshou Hu

    Corresponding author
    1. Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, P. R. China
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Correspondence to: Dr. Yingjie WEI, Dr. Shengshou HU
Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing 100037, P. R. China.
Tel.: 8610-88398494
Fax: 8610-88396050
E-mail: weiyingjiefw@126.com

Abstract

Although past studies observed the changes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in end-stage heart failure (HF) patients, a consistent and clear pattern of type-specific MMPs and/or TIMPs has yet to be further defined. In this study, proteomic approach of human protein antibody arrays was used to compare MMP and TIMP expression levels of left ventricular (LV) myocardial samples from end-stage HF patients due to dilated cardiomyopathy (DCM) with those from age- and sex- matched non-failing patients. Western blot analysis, immunohistochemistry and ELISA were used for validation of our results. We observed that MMP-10 and -7 abundance increased, accompanied by decreased TIMP-4 in DCM failing hearts (n= 8) compared with non-failing hearts (n= 8). The results were further validated in a cohort of 34 end-stage HF patients derived from three forms of cardiomyopathies. Cardiac and plasma MMP-10 levels were positively correlated with the LV end-diastolic dimension in this HF cohort. In addition, we observed that insulin-like growth factor-2 promoted MMP-10 production in neonatal rat cardiomyocytes. In conclusion, this study demonstrated a selective up-regulation of MMP-10 and -7 along with a discordant change of TIMP-4, and a positive correlation between MMP-10 levels and the degree of LV dilation in end-stage HF patients. Our findings suggest that type-specific dysregulation of MMPs and TIMPs is associated with LV remodelling in end-stage HF patients, and MMP-10 may act as a novel biomarker for LV remodelling.

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