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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

Temporal pattern of decorin protein levels during AAA development in mice.(A) A mouse model of AAA was induced by periaortic application of CaCl2. Saline application was used as a control. The mice were sacrificed 0, 3, 7, 14, 28, or 42 days after CaCl2 treatment. (B) Representative images showing aortic walls stained with hematoxylin and eosin (HE), elastica van-Gieson (EVG), or an antibody against decorin at the indicated time points after the application of saline (Control) or CaCl2 (AAA induction). The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and the elastin network (black), respectively. Localization of decorin is indicated by red staining. M: media, A: adventitia.
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pone.0120689.g001: Temporal pattern of decorin protein levels during AAA development in mice.(A) A mouse model of AAA was induced by periaortic application of CaCl2. Saline application was used as a control. The mice were sacrificed 0, 3, 7, 14, 28, or 42 days after CaCl2 treatment. (B) Representative images showing aortic walls stained with hematoxylin and eosin (HE), elastica van-Gieson (EVG), or an antibody against decorin at the indicated time points after the application of saline (Control) or CaCl2 (AAA induction). The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and the elastin network (black), respectively. Localization of decorin is indicated by red staining. M: media, A: adventitia.

Mentions: First, we analyzed a mouse model of AAA to evaluate decorin protein levels during the initiation, development, and progression of AAA. The mouse model was created by periaortic application of CaCl2 in the infrarenal aorta (Fig. 1A). After 3 days, the CaCl2 treatment induced infiltration of inflammatory cells. From 3 to 14 days, the elastic lamellae began to exhibit straightening and fragmentation. Inflammatory cell infiltration and the disruption of elastic layers continued and gradually increased up to 42 days (Fig. 1B). Consequently, 28 and 42 days after CaCl2 treatment, the infrarenal aortas of AAA mice exhibited significantly larger maximum diameters than the controls, which was consistent with our previous results [12].


Possible dual role of decorin in abdominal aortic aneurysm.

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

Temporal pattern of decorin protein levels during AAA development in mice.(A) A mouse model of AAA was induced by periaortic application of CaCl2. Saline application was used as a control. The mice were sacrificed 0, 3, 7, 14, 28, or 42 days after CaCl2 treatment. (B) Representative images showing aortic walls stained with hematoxylin and eosin (HE), elastica van-Gieson (EVG), or an antibody against decorin at the indicated time points after the application of saline (Control) or CaCl2 (AAA induction). The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and the elastin network (black), respectively. Localization of decorin is indicated by red staining. M: media, A: adventitia.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362951&req=5

pone.0120689.g001: Temporal pattern of decorin protein levels during AAA development in mice.(A) A mouse model of AAA was induced by periaortic application of CaCl2. Saline application was used as a control. The mice were sacrificed 0, 3, 7, 14, 28, or 42 days after CaCl2 treatment. (B) Representative images showing aortic walls stained with hematoxylin and eosin (HE), elastica van-Gieson (EVG), or an antibody against decorin at the indicated time points after the application of saline (Control) or CaCl2 (AAA induction). The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and the elastin network (black), respectively. Localization of decorin is indicated by red staining. M: media, A: adventitia.
Mentions: First, we analyzed a mouse model of AAA to evaluate decorin protein levels during the initiation, development, and progression of AAA. The mouse model was created by periaortic application of CaCl2 in the infrarenal aorta (Fig. 1A). After 3 days, the CaCl2 treatment induced infiltration of inflammatory cells. From 3 to 14 days, the elastic lamellae began to exhibit straightening and fragmentation. Inflammatory cell infiltration and the disruption of elastic layers continued and gradually increased up to 42 days (Fig. 1B). Consequently, 28 and 42 days after CaCl2 treatment, the infrarenal aortas of AAA mice exhibited significantly larger maximum diameters than the controls, which was consistent with our previous results [12].

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