Journal of Molecular and Cellular Cardiology
Volume 48, Issue 3 , Pages 445-453, March 2010

TIMPs and cardiac remodeling: ‘Embracing the MMP-independent-side of the family’

  • Davy Vanhoutte

      Affiliations

    • Vesalius Research Center (VRC), K.U. Leuven, Leuven, Belgium
    • Vesalius Research Center (VRC), VIB, Leuven, Belgium
    • Department of Cardiovascular Diseases, K.U.Leuven, Leuven, Belgium
  • ,
  • Stephane Heymans

      Affiliations

    • Center for Heart Failure Research, CARIM, University of Maastricht Medical Center, Department of Cardiology, PO BOX 5800, 6202 AZ Maastricht, The Netherlands
    • Corresponding Author InformationCorresponding author. Tel.: +31433877097; fax: +31433871055.

Received 11 May 2009; received in revised form 21 September 2009; accepted 21 September 2009. published online 05 October 2009.

Abstract 

Unraveling the biological role of tissue inhibitors of metalloproteinases (TIMPs) during cardiac remodeling and the progression of heart failure has proven to be an enormous challenge. Remodeling of the cardiac extracellular matrix (ECM), regulated by matrix metalloproteinases (MMPs) and their endogenous inhibitors, TIMPs, is a well-established paradigm in cardiac health and disease. Originally, TIMPs were thought to function exclusively as endogenous inhibitors of MMP activity, thereby fine-tuning MMP-mediated ECM degradation and numerous related processes. However, during the last two decades, the concept of MMP-independent TIMP-mediated receptor signaling and regulation of cell fate has emerged. Although our current knowledge is still limited, in this review, we highlight some of the novel data, illustrating the MMP-independent biological properties of the four TIMP family members. Moreover, we discuss how these cell-specific insights may contribute to the process of cardiac remodeling, disease and failure. Finally, we identify where additional research is needed that will codetermine the possible future of TIMPs as therapeutic targets.

Keywords: Tissue inhibitors of matrix metalloproteinase (TIMP), Matrix metalloproteinases (MMPs), Cardiac remodeling, Heart failure, Therapy, Receptor signaling, Endothelial cell, Angiogenesis, Fibroblast, Cardiomyocytes, Inflammation, Review

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PII: S0022-2828(09)00412-X

doi:10.1016/j.yjmcc.2009.09.013

Journal of Molecular and Cellular Cardiology
Volume 48, Issue 3 , Pages 445-453, March 2010