Heart Failure Reviews

, Volume 17, Issue 4, pp 693–706

Tissue inhibitor of metalloproteinases (TIMPs) in heart failure

  • Linn Moore
  • Dong Fan
  • Ratnadeep Basu
  • Vijay Kandalam
  • Zamaneh Kassiri
Article

DOI: 10.1007/s10741-011-9266-y

Cite this article as:
Moore, L., Fan, D., Basu, R. et al. Heart Fail Rev (2012) 17: 693. doi:10.1007/s10741-011-9266-y

Abstract

Remodeling of the myocardium and the extracellular matrix (ECM) occurs in heart failure irrespective of its initial cause. The ECM serves as a scaffold to provide structural support as well as housing a number of cytokines and growth factors. Hence, disruption of the ECM will result in structural instability as well as activation of a number of signaling pathways that could lead to fibrosis, hypertrophy, and apoptosis. The ECM is a dynamic entity that undergoes constant turnover, and the integrity of its network structure is maintained by a balance in the function of matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). In heart disease, levels of MMPs and TIMPs are altered resulting in an imbalance between these two families of proteins. In this review, we will discuss the structure, function, and regulation of TIMPs, their MMP-independent functions, and their role in heart failure. We will review the knowledge that we have gained from clinical studies and animal models on the contribution of TIMPs in the development and progression of heart disease. We will further discuss how ECM molecules and regulatory genes can be used as biomarkers of disease in heart failure patients.

Keywords

Heart failure Extracellular matrix Remodeling Tissue inhibitor of metalloproteinases Matrix metalloproteinases 

Abbreviations

ADAM

A disintegrin and matrix metalloproteinase

CITP

Carboxy-terminal telopeptide of collagen type I

DCM

Dilated cardiomyopathy

ECM

Extracellular Matrix

FGF

Fibroblast growth factor

HB-EGF

Heparin-bound epidermal growth factor

IL

Interleukin

LV

Left ventricle

MI

Myocardial infarction

MMP

Matrix metalloproteinase

MT-MMP

Membrane-type MMP

PDGF

Platelet-derived growth factor

PICP

Procollagen type I carboxy-terminal propeptide

PINP

Procollagen type I amino-terminal propeptides

PIIINP

Procollagen type III amino-terminal pro-peptide

TIMP

Tissue inhibitor metalloproteinase

TGFβ

Transforming growth factor-beta

TNFα

Tumor necrosis factor-alpha

VEGF

Vascular endothelial growth factor

WT

Wild-type

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Linn Moore
    • 1
  • Dong Fan
    • 1
  • Ratnadeep Basu
    • 1
  • Vijay Kandalam
    • 1
  • Zamaneh Kassiri
    • 1
  1. 1.Department of Physiology, Cardiovascular Research Centre, Mazankowski Alberta Heart InstituteUniversity of AlbertaEdmontonCanada

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