Role of transglutaminases in cuff-induced atherosclerotic lesion formation in femoral arteries of ApoE3 Leiden mice

Matlung, Hanke L.; VanBavel, Ed; van den Akker, Jeroen; de Vries, Carlie J.M.; Bakker, Erik N.T.P.

doi:10.1016/j.atherosclerosis.2010.07.054

« Previous Next »Atherosclerosis
Volume 213, Issue 1 , Pages 77-84, November 2010

Role of transglutaminases in cuff-induced atherosclerotic lesion formation in femoral arteries of ApoE3 Leiden mice

Hanke L. Matlung
- Department of Biomedical Engineering and Physics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands
Ed VanBavel
- Department of Biomedical Engineering and Physics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands
Jeroen van den Akker
- Department of Biomedical Engineering and Physics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands
Carlie J.M. de Vries
- Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands
Erik N.T.P. Bakker
- Department of Biomedical Engineering and Physics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands
- Corresponding author. Tel.: +31 20 5665190; fax: +31 20 6917233.

Received 19 January 2010; received in revised form 14 July 2010; accepted 27 July 2010. published online 02 September 2010.

Abstract

Transglutaminases play an important role in vascular remodeling, calcification, cell adhesion and endothelial barrier function. In this study we investigate the influence of combined inhibition of both tissue-type transglutaminase (TG2) and the plasma transglutaminase FXIIIA on early lesion development.

Methods

A cuff was placed around the femoral arteries of ApoE3 Leiden mice while fed a Western type diet to induce atherosclerotic lesion development. An osmotic minipump was placed in the intraperitoneal cavity containing an irreversible inhibitor of TG2 and FXIIIA activity ((1,3,4,5-tetramethyl-2-[(2-oxopropyl)thio]imidazolium chloride, Zedira). Atherosclerotic lesion composition was analyzed using immunohistochemistry and RT-PCR.

Results

Inhibition of transglutaminases did not influence lesion size or geometric remodeling of the vessels. However, systemic transglutaminase inhibition resulted in 41% less macrophage infiltrate in the media of the vessels. Additional in vitro experiments on HL60 cells confirmed a decreased migratory response during transglutaminase inhibition.

Conclusion

Inhibition of TG2 and FXIIIA during early development of lesions reduced the macrophage content in the media of atherosclerotic vessels, while not affecting lesion size or geometric remodeling.

Keywords: Transglutaminases, Factor XIII, Macrophages