Cellular FXIII in Human Macrophage-Derived Foam Cells

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Abstract
Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human macrophages into foam cells. ELISA and Western blotting techniques revealed that the transformation of macrophages into foam cells elevated the intracellular FXIII-A content. This phenomenon seems specific for macrophage-derived foam cells; the transformation of vascular smooth muscle cells into foam cells fails to induce a similar effect. FXIII-A containing macrophages are abundant in the atherosclerotic plaque and FXIII-A is also present in the extracellular compartment. The protein cross-linking activity of FXIII-A in the plaque was demonstrated using an antibody labeling the iso-peptide bonds. Cells showing combined staining for FXIII-A and oxLDL in tissue sections demonstrated that FXIII-A-containing macrophages within the atherosclerotic plaque are also transformed into foam cells. Such cells may contribute to the formation of lipid core and the plaque structurization.
Funding Information
  • National Research, Development, and Innovation Office (NKFIH) (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)
  • European Union and the European Regional Development Fund (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)
  • Hungarian Academy of Science (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)
  • Eötvös Loránd Research Network (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)
  • University of Aberdeen Development TRUST (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)
  • British Heart Foundation (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)
  • British Heart Foundation Fellowship (K129287, 11014, 11003, RS2015 006, PG/15/82/31721, FS/11/2/28579)

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