Possible dual role of decorin in abdominal aortic aneurysm.

Koshiro Ueda,Takasuke Harada,Koichi Yoshimura,Osamu Yamashita,Kimikazu Hamano,Noriyasu Morikage,Utako Yokoyama

doi:10.1371/journal.pone.0120689

Koshiro Ueda, Takasuke Harada + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0120689

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Journal: PloS one	Publication Date: Mar 17, 2015
Citations: 14	License type: CC BY 4.0

Affiliation: Yamaguchi University

Abstract

Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation, which leads to pathological remodeling of the extracellular matrix. Decorin, a small leucine-rich repeat proteoglycan, has been suggested to regulate inflammation and stabilize the extracellular matrix. Therefore, the present study investigated the role of decorin in the pathogenesis of AAA. Decorin was localized in the aortic adventitia under normal conditions in both mice and humans. AAA was induced in mice using CaCl2 treatment. Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers. Local administration of exogenous decorin prevented the development of CaCl2-induced AAA. However, decorin was highly expressed in the degenerative lesions of human AAA walls, and this expression positively correlated with matrix metalloproteinase (MMP)-9 expression. In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages. The results suggest that decorin plays a dual role in AAA. Adventitial decorin in normal aorta may protect against the development of AAA, but macrophages expressing decorin in AAA walls may facilitate the progression of AAA by up-regulating MMP-9 secretion.

Highlights

Because our in vivo findings suggested that decorin inhibits matrix metalloproteinase (MMP)-9 expression in the aortic wall, we investigated whether decorin negatively regulates MMP-9 protein secretion in vascular smooth muscle cells (VSMCs), one of the major cell types of the aortic wall (Fig. 3A)
To understand the conflicting findings regarding the role of decorin in aortic walls, we investigated whether decorin positively regulates MMP-9 secretion in macrophages, the major inflammatory cell-type secreting MMP-9 in Abdominal aortic aneurysm (AAA) walls [9,17] (Fig. 5A)
We found that decorin is expressed in abundance in progressed AAA lesions in both mice and humans, and its expression is accompanied by macrophage infiltration, tissue damage, and elevated MMP-9 expression

Summary

Introduction

Extracellular matrix proteins are major constituents of the vascular wall and can potentially interact with a variety of vascular cells Extracellular matrix proteins, such as periostin and tenascin C, have been suggested to play important roles in the pathogenesis of AAA [10,11,12]. A previous study showed that reduced decorin expression is associated with a high risk of aortic rupture in a mouse model of AAA [16]. These findings led us to hypothesize that decorin plays a crucial role in the pathogenesis of AAA. We show that decorin has both tissue-protective and proinflammatory properties, depending on the context in which it is expressed

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