Histochemistry and Cell Biology

, Volume 126, Issue 3, pp 335–342

Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology

Authors

  • Ilpo Koskivirta
    • Department of Medical Biochemistry and Molecular BiologyUniversity of Turku
    • Department of Medicine, Turku University Central HospitalUniversity of Turku
  • Otto Rahkonen
    • Department of Medical Biochemistry and Molecular BiologyUniversity of Turku
    • Department of PediatricsUniversity of Helsinki
  • Mikko Mäyränpää
    • Wihuri Research Institute
  • Sari Pakkanen
    • Department of Medical Biochemistry and Molecular BiologyUniversity of Turku
  • Michael Husheem
    • Department of Anatomy University of Turku
  • Annele Sainio
    • Department of Medical Biochemistry and Molecular BiologyUniversity of Turku
  • Harri Hakovirta
    • Department of Surgery University of Turku
  • Jukka Laine
    • Department of PathologyUniversity of Turku
  • Eero Jokinen
    • Department of PediatricsUniversity of Helsinki
  • Eero Vuorio
    • Department of Medical Biochemistry and Molecular BiologyUniversity of Turku
  • Petri Kovanen
    • Wihuri Research Institute
    • Department of Medical Biochemistry and Molecular BiologyUniversity of Turku
    • Department of Medicine, Turku University Central HospitalUniversity of Turku
Original paper

DOI: 10.1007/s00418-006-0163-8

Cite this article as:
Koskivirta, I., Rahkonen, O., Mäyränpää, M. et al. Histochem Cell Biol (2006) 126: 335. doi:10.1007/s00418-006-0163-8

Abstract

Tissue inhibitors of matrix metalloproteinases (TIMPs) comprise a family of four members, of which TIMP4 is characterized by being primarily restricted to cardiovascular structures. We demonstrate with immunohistochemical analysis of healthy human tissue that TIMP4 is present in medial smooth muscle cells and adventitial capillaries of arteries as well as in cardiomyocytes. Animal studies have suggested a role for TIMP4 in several inflammatory diseases and cardiovascular pathologies. We therefore examined whether TIMP4 is involved in human inflammatory cardiovascular disorders, specifically atherosclerosis, giant cell arteritis and chronic rejection of heart allografts. TIMP4 was most clearly visible in cardiovascular tissue areas populated by abundant inflammatory cells, mainly macrophages and CD3+ T cells. Using western blotting and immunocytochemistry, human blood derived lymphocytes, monocytes/macrophages and mast cells were shown to produce TIMP4. In advanced atherosclerotic lesions, TIMP4 was detected around necrotic lipid cores, whereas TIMP3 and caspase 3 resided within and around the core regions, indicating different roles for TIMP3 and TIMP4 in inflammation-induced apoptosis and in matrix turnover. In conclusion, the data demonstrate upregulation of TIMP4 in human cardiovascular disorders exhibiting inflammation, suggesting its future use as a novel systemic marker for vascular inflammation.

Keywords

TIMP4InflammationAtherosclerosisGiant cell arteritisHeart allograft rejection

Copyright information

© Springer-Verlag 2006