Thrombin upregulates tissue transglutaminase in endothelial cells: a potential role for tissue transglutaminase in stability of atherosclerotic plaque

G. C. Auld, H. Ritchie, L. A. Robbie, Nuala Ann Booth

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Atherosclerosis is characterized by thickening of the vessel wall, smooth muscle cell proliferation, macrophage infiltration, and deposition of a fibrin network. Transglutaminases are a family of enzymes catalyzing the formation of stable covalent cross-links between proteins. Here, we show that tissue transglutaminase (tTG) synthesis by human umbilical vein endothelial cells is upregulated by thrombin, the serine protease that causes fibrin formation and many cellular inflammatory effects. Thrombin upregulated tTG 2-fold at the mRNA and protein level. Cellular cross-linking activity was increased to an even greater extent; antibody to tTG neutralized the increased activity. The effect on tTG expression required active thrombin and was mediated mainly through protease-activated receptor-1, a thrombin receptor. Increased tTG antigen and activity were evident in human umbilical vein endothelial cells and extracellular matrix in situ. Thrombin treatment also led to a cellular redistribution of tTG. Normal vessel wall stained positively for tTG in the smooth muscle cells and in the subendothelium. The intensity of staining increased in vessel walls with plaque, where there was a striking increase in tTG in the smooth muscle cells immediately below the plaque. These studies indicate a role for tTG in the stabilization of atherosclerotic plaques and suggest that its local expression can be controlled by thrombin.

Original languageEnglish
Pages (from-to)1689-1694
Number of pages5
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume21
Issue number10
DOIs
Publication statusPublished - Oct 2001

Keywords

  • thrombin
  • transglutaminase
  • atherosclerosis
  • endothelium
  • PLASMINOGEN-ACTIVATOR-INHIBITOR
  • CROSS-LINKING ENZYMES
  • SMOOTH-MUSCLE CELLS
  • II TRANSGLUTAMINASE
  • MOLECULAR-CLONING
  • EXPRESSION
  • FIBRONECTIN
  • RECEPTOR
  • SUBSTRATE
  • ADHESION

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