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Possible dual role of decorin in abdominal aortic aneurysm.

Ueda K, Yoshimura K, Yamashita O, Harada T, Morikage N, Hamano K - PLoS ONE (2015)

Bottom Line: Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Role of decorin in VSMC secretion of MMP-9.(A) Cultured rat vascular smooth muscle cells (VSMCs) were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. Protein levels of MMP-9 and MMP-2 in the conditioned media were determined by gelatin zymography. (B) Representative results are shown. (C-D) Cultured rat VSMCs were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses for MMP-9 (C) and MMP-2 (D) are shown. Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.
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pone.0120689.g003: Role of decorin in VSMC secretion of MMP-9.(A) Cultured rat vascular smooth muscle cells (VSMCs) were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. Protein levels of MMP-9 and MMP-2 in the conditioned media were determined by gelatin zymography. (B) Representative results are shown. (C-D) Cultured rat VSMCs were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses for MMP-9 (C) and MMP-2 (D) are shown. Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.

Mentions: Because our in vivo findings suggested that decorin inhibits MMP-9 expression in the aortic wall, we investigated whether decorin negatively regulates MMP-9 protein secretion in VSMCs, one of the major cell types of the aortic wall (Fig. 3A). Under basal conditions, MMP-2 was readily detectable in the conditioned media of VSMCs, but MMP-9 was nearly undetectable. However, the VSMCs secreted appreciable levels of MMP-9 in response to LPS treatment. Interestingly, this LPS-induced up-regulation of MMP-9 secretion was abrogated by pre-treatment with exogenous decorin in a dose-dependent manner (Fig. 3B-C). Neither LPS nor decorin affected the secretion of MMP-2, which suggests that cell viability was preserved during the experiments (Fig. 3D). These data demonstrate that decorin plays a role in protecting VSMCs from inflammatory insults by inhibiting the up-regulation of MMP-9.


Possible dual role of decorin in abdominal aortic aneurysm.

Ueda K, Yoshimura K, Yamashita O, Harada T, Morikage N, Hamano K - PLoS ONE (2015)

Role of decorin in VSMC secretion of MMP-9.(A) Cultured rat vascular smooth muscle cells (VSMCs) were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. Protein levels of MMP-9 and MMP-2 in the conditioned media were determined by gelatin zymography. (B) Representative results are shown. (C-D) Cultured rat VSMCs were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses for MMP-9 (C) and MMP-2 (D) are shown. Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4362951&req=5

pone.0120689.g003: Role of decorin in VSMC secretion of MMP-9.(A) Cultured rat vascular smooth muscle cells (VSMCs) were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. Protein levels of MMP-9 and MMP-2 in the conditioned media were determined by gelatin zymography. (B) Representative results are shown. (C-D) Cultured rat VSMCs were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses for MMP-9 (C) and MMP-2 (D) are shown. Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.
Mentions: Because our in vivo findings suggested that decorin inhibits MMP-9 expression in the aortic wall, we investigated whether decorin negatively regulates MMP-9 protein secretion in VSMCs, one of the major cell types of the aortic wall (Fig. 3A). Under basal conditions, MMP-2 was readily detectable in the conditioned media of VSMCs, but MMP-9 was nearly undetectable. However, the VSMCs secreted appreciable levels of MMP-9 in response to LPS treatment. Interestingly, this LPS-induced up-regulation of MMP-9 secretion was abrogated by pre-treatment with exogenous decorin in a dose-dependent manner (Fig. 3B-C). Neither LPS nor decorin affected the secretion of MMP-2, which suggests that cell viability was preserved during the experiments (Fig. 3D). These data demonstrate that decorin plays a role in protecting VSMCs from inflammatory insults by inhibiting the up-regulation of MMP-9.

Bottom Line: Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan.

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.

No MeSH data available.


Related in: MedlinePlus