Vena cava and aortic smooth muscle cells express transglutaminases 1 and 4 in addition to transglutaminase 2

Am J Physiol Heart Circ Physiol. 2012 Apr 1;302(7):H1355-66. doi: 10.1152/ajpheart.00918.2011. Epub 2012 Feb 3.


Transglutaminase (TG) function facilitates several vascular processes and diseases. Although many of these TG-dependent vascular processes have been ascribed to the function of TG2, TG2 knockout mice have a mild vascular phenotype. We hypothesized that TGs besides TG2 exist and function in the vasculature. Biotin-pentylamide incorporation, a measure of general TG activity, was similar in wild-type and TG2 knockout mouse aortae, and the general TG inhibitor cystamine reduced biotin-pentylamine incorporation to a greater extent than the TG2-specific inhibitor Z-DON, indicating the presence of other functional TGs. Additionally, 5-hydroxytryptamine-induced aortic contraction, a TG-activity-dependent process, was decreased to a greater extent by general TG inhibitors vs. Z-DON (maximum contraction: cystamine = abolished, monodansylcadaverine = 28.6 ± 14.9%, and Z-DON = 60.2 ± 15.2% vehicle), providing evidence for the importance of TG2-independent activity in the vasculature. TG1, TG2, TG4, and Factor XIII (FXIII) mRNA in rat aortae and vena cavae was detected by RT-PCR. Western analysis detected TG1 and TG4, but not FXIII, in rat aortae and vena cavae and in TG2 knockout and wild-type mouse aortae. Immunostaining confirmed the presence of TG1, TG2, and TG4 in rat aortae and vena cavae, notably in smooth muscle cells; FXIII was absent. K5 and T26, FITC-labeled peptide substrates specific for active TG1 and TG2, respectively, were incorporated into rat aortae and vena cavae and wild-type, but not TG2 knockout, mouse aortae. These studies demonstrate that TG2-independent TG activity exists in the vasculature and that TG1 and TG4 are expressed in vascular tissues.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / enzymology*
  • Blotting, Western
  • Cadaverine / analogs & derivatives
  • Cadaverine / antagonists & inhibitors
  • Cross-Linking Reagents
  • Enzyme Inhibitors / pharmacology
  • Factor XIII / biosynthesis
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / biosynthesis*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Myocytes, Smooth Muscle / enzymology*
  • Protein Glutamine gamma Glutamyltransferase 2
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Transglutaminases / antagonists & inhibitors
  • Transglutaminases / biosynthesis*
  • Vena Cava, Superior / cytology
  • Vena Cava, Superior / enzymology


  • Cross-Linking Reagents
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Tgm2 protein, rat
  • Factor XIII
  • transglutaminase 4
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • transglutaminase 1
  • GTP-Binding Proteins
  • Fluorescein-5-isothiocyanate
  • monodansylcadaverine
  • Cadaverine