Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cellular FXIII in Human Macrophage Derived Foam Cells

Laura Somodi
ORCID logo ,
Emőke Horváth
,
Helga Bárdos
,
Barbara Baráth
,
Dávid Pethő
ORCID logo ,
Éva Katona
ORCID logo ,
József Balla
,
Nicola J Mutch
ORCID logo ,
László Muszbek
* ORCID logo
Version 1 : Received: 30 January 2023 / Approved: 31 January 2023 / Online: 31 January 2023 (10:23:56 CET)
Version 2 : Received: 1 February 2023 / Approved: 2 February 2023 / Online: 2 February 2023 (11:52:20 CET)

A peer-reviewed article of this Preprint also exists.

Somodi, L.; Horváth, E.; Bárdos, H.; Baráth, B.; Pethő, D.; Katona, É.; Balla, J.; Mutch, N.J.; Muszbek, L. Cellular FXIII in Human Macrophage-Derived Foam Cells. Int. J. Mol. Sci. 2023, 24, 4802. Somodi, L.; Horváth, E.; Bárdos, H.; Baráth, B.; Pethő, D.; Katona, É.; Balla, J.; Mutch, N.J.; Muszbek, L. Cellular FXIII in Human Macrophage-Derived Foam Cells. Int. J. Mol. Sci. 2023, 24, 4802.

Abstract

The potentially active A subunit of coagulation factor XIII (FXIII-A) is an intracellular transglutaminase expressed in various cell types including platelets and monocytes/macrophages. It is involved in stabilizing protein structures by cross-linking through Nε-(?-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque and are important in determining its structural/functional features. Two of their important functions are the accumulation of oxidized LDL in the lipid core, and by cross-linking structural proteins they may stabilize the plaque and protect the thrombi of atherogenic origin against fibrinolytic degradation. It is important to know whether these functions operate in parallel utilizing the same cellular compartments. First, we showed that monocyte-derived human macrophages significantly increase their FXIII-A content when up-taking oxidized LDL. This phenomenon is very likely independent of the process of transformation into foam cells, as the transformation of vascular smooth muscle cells into foam cells fails to result in the expression of FXIII-A. FXIII containing macrophage-like cells are abundant in the plaque and FXIII-A is also present in the extracellular core. Several cells co-stained for FXIII-A and for Oil Red O suggest that expression of FXIII-A and lipid up-take are common features of macrophages present in the atherosclerotic plaque.

Keywords

factor XIII, foam cells, macrophages, vascular smooth muscle cells, oxidized LDL, enzyme-modified LDL, transglutaminase, atherosclerotic plaque, cross-linking

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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