This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Auld, G. C. Articles by Booth, N. A. Search for Related Content PubMed PubMed Citation Articles by Auld, G. C. Articles by Booth, N. A. Pubmed/NCBI databases Substance via MeSH Related Collections Fibrinogen/fibrin Thrombin Other Vascular biology Gene expression Other arteriosclerosis

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1689.)
© 2001 American Heart Association, Inc.

Thrombosis

Thrombin Upregulates Tissue Transglutaminase in Endothelial Cells

A Potential Role for Tissue Transglutaminase in Stability of Atherosclerotic Plaque

Gillian C. Auld; Helen Ritchie; Linda A. Robbie; Nuala A. Booth

Departments of Molecular and Cell Biology (G.C.A., H.R., L.A.R., N.A.B.) and Medicine and Therapeutics (L.A.R.), University of Aberdeen, Institute of Medical Sciences, Aberdeen, UK.

Correspondence to Nuala A. Booth, PhD, Department of Molecular and Cell Biology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. E-mail n.a.booth{at}abdn.ac.uk

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.

Key Words: thrombin • transglutaminase • atherosclerosis • endothelium

This article has been cited by other articles:

				K. A. Johnson, M. Polewski, and R. A. Terkeltaub Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells Circ. Res., March 14, 2008; 102(5): 529 - 537. [Abstract] [Full Text] [PDF]

				G. Mazooz, T. Mehlman, T.-S. Lai, C. S. Greenberg, M. W. Dewhirst, and M. Neeman Development of Magnetic Resonance Imaging Contrast Material for In vivo Mapping of Tissue Transglutaminase Activity Cancer Res., February 15, 2005; 65(4): 1369 - 1375. [Abstract] [Full Text] [PDF]

				K. Mohan, D. Pinto, and T. B. Issekutz Identification of Tissue Transglutaminase as a Novel Molecule Involved In Human CD8+ T Cell Transendothelial Migration J. Immunol., September 15, 2003; 171(6): 3179 - 3186. [Abstract] [Full Text] [PDF]