Transglutaminases locate to calcified areas in advanced human atherosclerotic lesions

Abstract

We investigated the involvement of the two major transglutaminases (TGs), tissue transglutaminase (TG2) and factor XIIIa (FXIIIA), in human atherosclerotic calcification. Methods Cross‐sections of human carotid atherosclerotic plaques were stained for TG2, FXIIIA, the TG‐induced cross‐link and macrophage marker CD68. The correlation of these staining patterns to calcified areas throughout the specimens was tested by multi‐scale 3D mapping of the microscopic images to μCT images. Results The TG‐induced cross‐link was found in 64 ± 8% (mean ± SEM) of the analyzed areas inside the plaques. Calcified areas correlated with this cross‐link (p<0.001). FXIIIA was found to be the dominant transglutaminase (56 ± 10% of the cross‐link‐positive areas), as compared to 11 ± 3% for TG2. Both transglutaminases correlated with the cross‐link (p=<0.001 and p=0.002 respectively). Staining for FXIIIA correlated with CD68 (p<0.001) on tissue level and also co‐localized with CD68 positive cells as shown by double immunofluorescent staining. Conclusion Areas of calcification locate to the presence and activity of transglutaminases in human atherosclerotic arteries. FXIIIA is dominantly present over TG2 in these plaques and may be derived from local macrophages. Supported by the Netherlands Heart Foundation (NHS 2001T038).