title: Calcification locates to transglutaminases in advanced human atherosclerotic lesions.
abstract: Transglutaminases play an important role in vascular smooth muscle cell-induced calcification in vitro. In this study, we determined whether these enzymes are also involved in human atherosclerotic calcification using nine carotid artery specimens obtained at endarterectomy. Sections of the carotid artery specimens were registered to micro-computed tomography images and stained for tissue-type transglutaminase, plasma transglutaminase factor XIIIA (FXIIIA), the N(epsilon)(gamma-glutamyl)lysine cross-link, and the macrophage marker CD68. Ex vivo micro-computed tomography revealed extensive calcification, which significantly correlated with the cross-link. FXIIIA was found to be the dominant transglutaminase, rather than tissue-type transglutaminase, although staining of both transglutaminases correlated with the cross-link. Staining for FXIIIA colocalized with CD68 at both the cellular and tissue level. In conclusion, areas of calcification locate to the presence and activity of transglutaminases in human atherosclerotic arteries. FXIIIA seems to be the dominant transglutaminase and may be derived from local macrophages. These results are consistent with the hypothesis that transglutaminases participate in the calcification process of human atherosclerotic arteries.
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hanke L
authors.initials: HL
authors.lastname: Matlung
authors.forename: Harald C
authors.initials: HC
authors.lastname: Groen
authors.forename: Judith
authors.initials: J
authors.lastname: de Vos
authors.forename: Theo
authors.initials: T
authors.lastname: van Walsum
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.forename: Jolanda J
authors.initials: JJ
authors.lastname: Wentzel
authors.forename: Ed
authors.initials: E
authors.lastname: Vanbavel
authors.forename: Erik N T P
authors.initials: EN
authors.lastname: Bakker
mesh_terms: D050197:Atherosclerosis / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D002114:Calcinosis / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D011503:Transglutaminases
chemical_list: D011503:Transglutaminases