Increased tissue transglutaminase expression in human atherosclerotic coronary arteries

Background and objective Transglutaminase 2 (TGase 2) is a calcium-dependent cross-linking enzyme that catalyzes a covalent iso-peptide bond between two proteins. Interestingly, this catalysis can activate the nuclear factor-kappa B (NF-kappa B) through the polymerization of the inhibitory protein of NF-kappa B (I-kappa B). The objective of the present study was to investigate the expression of TGase 2 in the human atherosclerotic human coronary artery, and the possible roles of TGase 2 in NF-kappa B activation. Methods and results We explored whether expressions of TGase 2 and NF-kappa B are associated in atherosclerosis. Using human samples, we found that TGase 2 was markedly higher than normal in the neointimal tissue of atherosclerotic coronary arteries with atherosclerosis progression. TGase 2 activity was also increased approximately two-fold in the atherosclerotic vascular wall. In immunofluorescence analysis, NF-kappa B, COX-2, and TNF-alpha were co-localized at TGase 2-positive neointimal smooth muscle cells. A promoter assay test showed that NF-kappa B activity increased in both the human monocyte and human breast carcinoma cell by TGase 2, and that TGase 2-mediated NF-kappa B activation was reversed by TGase 2 siRNA. Conclusion According to these results, we suggest that TGase 2 may function as an activator in the NF-kappa B pathway; this effect may occur in the atherosclerotic vessel wall. Coron Artery Dis 19:459-468 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.