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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

Expression of decorin in human AAA.(A-B) Protein samples were obtained from the aortic walls of human AAA specimens (n = 47) and non-aneurysmal specimens (Control, n = 4). Representative results from western blot detection of decorin are shown (A) with the corresponding quantitative analysis (B). GAPDH served as an internal control. Data are mean ± SD. *p<0.05 compared to Control. (C) The correlation between the protein levels of decorin and MMP-9 was examined and the quantitative analysis is shown (Pearson r = 0.68, n = 51, p< 0.001). (D) The correlation between the protein levels of decorin and TGF-β was examined and the quantitative analysis is shown (Pearson r = 0.39, n = 51, p< 0.01). (E) Representative histological and immunohistochemical stains are shown for human AAA wall specimens. The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and elastin network (black), respectively. The localization of decorin and MMP-9 is indicated by red staining. M: media, A: adventitia. (F-G) Representative images of immunofluorescence staining for decorin (red) and CD68 (macrophage marker, green, F) or α-smooth muscle actin (α-SMA) (smooth muscle cell marker, green, G). Yellow in the merged images indicates overlapping localization of the red and green signals.
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pone.0120689.g004: Expression of decorin in human AAA.(A-B) Protein samples were obtained from the aortic walls of human AAA specimens (n = 47) and non-aneurysmal specimens (Control, n = 4). Representative results from western blot detection of decorin are shown (A) with the corresponding quantitative analysis (B). GAPDH served as an internal control. Data are mean ± SD. *p<0.05 compared to Control. (C) The correlation between the protein levels of decorin and MMP-9 was examined and the quantitative analysis is shown (Pearson r = 0.68, n = 51, p< 0.001). (D) The correlation between the protein levels of decorin and TGF-β was examined and the quantitative analysis is shown (Pearson r = 0.39, n = 51, p< 0.01). (E) Representative histological and immunohistochemical stains are shown for human AAA wall specimens. The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and elastin network (black), respectively. The localization of decorin and MMP-9 is indicated by red staining. M: media, A: adventitia. (F-G) Representative images of immunofluorescence staining for decorin (red) and CD68 (macrophage marker, green, F) or α-smooth muscle actin (α-SMA) (smooth muscle cell marker, green, G). Yellow in the merged images indicates overlapping localization of the red and green signals.

Mentions: To determine whether these findings are applicable to humans, we examined decorin protein levels in human AAA specimens. Because we obtained the human AAA specimens from patients who had undergone open surgery, the specimens represented progressed lesions rather than initial lesions. Thus, these lesions most likely correspond to the mouse AAA specimens 42 days after CaCl2 treatment. As expected, decorin expression was greatly elevated in the human AAA walls compared to non-aneurysmal aortic walls (Controls) (Fig. 4A-B). MMP-9 expression was also highly elevated in the human AAA walls, as reported previously [26,27]. Interestingly, decorin protein levels positively correlated with MMP-9 protein levels in human specimens (Fig. 4C). TGF-β protein, a possible stabilizer of extracellular matrix in AAA [28] also positively correlated with decorin protein levels in human aortic specimens (Fig. 4D).


Possible dual role of decorin in abdominal aortic aneurysm.

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

Expression of decorin in human AAA.(A-B) Protein samples were obtained from the aortic walls of human AAA specimens (n = 47) and non-aneurysmal specimens (Control, n = 4). Representative results from western blot detection of decorin are shown (A) with the corresponding quantitative analysis (B). GAPDH served as an internal control. Data are mean ± SD. *p<0.05 compared to Control. (C) The correlation between the protein levels of decorin and MMP-9 was examined and the quantitative analysis is shown (Pearson r = 0.68, n = 51, p< 0.001). (D) The correlation between the protein levels of decorin and TGF-β was examined and the quantitative analysis is shown (Pearson r = 0.39, n = 51, p< 0.01). (E) Representative histological and immunohistochemical stains are shown for human AAA wall specimens. The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and elastin network (black), respectively. The localization of decorin and MMP-9 is indicated by red staining. M: media, A: adventitia. (F-G) Representative images of immunofluorescence staining for decorin (red) and CD68 (macrophage marker, green, F) or α-smooth muscle actin (α-SMA) (smooth muscle cell marker, green, G). Yellow in the merged images indicates overlapping localization of the red and green signals.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4362951&req=5

pone.0120689.g004: Expression of decorin in human AAA.(A-B) Protein samples were obtained from the aortic walls of human AAA specimens (n = 47) and non-aneurysmal specimens (Control, n = 4). Representative results from western blot detection of decorin are shown (A) with the corresponding quantitative analysis (B). GAPDH served as an internal control. Data are mean ± SD. *p<0.05 compared to Control. (C) The correlation between the protein levels of decorin and MMP-9 was examined and the quantitative analysis is shown (Pearson r = 0.68, n = 51, p< 0.001). (D) The correlation between the protein levels of decorin and TGF-β was examined and the quantitative analysis is shown (Pearson r = 0.39, n = 51, p< 0.01). (E) Representative histological and immunohistochemical stains are shown for human AAA wall specimens. The luminal surface is oriented toward the top of each panel. HE and EVG stains depict cell nuclei (blue-black) and elastin network (black), respectively. The localization of decorin and MMP-9 is indicated by red staining. M: media, A: adventitia. (F-G) Representative images of immunofluorescence staining for decorin (red) and CD68 (macrophage marker, green, F) or α-smooth muscle actin (α-SMA) (smooth muscle cell marker, green, G). Yellow in the merged images indicates overlapping localization of the red and green signals.
Mentions: To determine whether these findings are applicable to humans, we examined decorin protein levels in human AAA specimens. Because we obtained the human AAA specimens from patients who had undergone open surgery, the specimens represented progressed lesions rather than initial lesions. Thus, these lesions most likely correspond to the mouse AAA specimens 42 days after CaCl2 treatment. As expected, decorin expression was greatly elevated in the human AAA walls compared to non-aneurysmal aortic walls (Controls) (Fig. 4A-B). MMP-9 expression was also highly elevated in the human AAA walls, as reported previously [26,27]. Interestingly, decorin protein levels positively correlated with MMP-9 protein levels in human specimens (Fig. 4C). TGF-β protein, a possible stabilizer of extracellular matrix in AAA [28] also positively correlated with decorin protein levels in human aortic specimens (Fig. 4D).

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