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

Abstract：

UNLABELLED: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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Matlung HL,VanBavel E,van den Akker J,de Vries CJ,Bakker EN

doi

10.1016/j.atherosclerosis.2010.07.054

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

77-84

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(10)00599-X

journal_volume

213

pub_type

杂志文章

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