Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm.

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Presentation transcript:

Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm model Akiko Tanaka, MD, Tomomi Hasegawa, MD, PhD, Keisuke Morimoto, MD, Wulan Bao, MD, Jie Yu, MD, Yutaka Okita, MD, PhD, Yasuhiko Tabata, PhD, DMedSci, DPharm, Kenji Okada, MD, PhD Journal of Vascular Surgery Volume 60, Issue 3, Pages 749-758 (September 2014) DOI: 10.1016/j.jvs.2013.07.013 Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 1 A, The in vitro controlled release test of ascorbic acid over time. B, The in vivo controlled release test of ascorbic acid over time. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 2 A, The photographs show treated lesions of abdominal aorta at 4 weeks in each group. Group A, Ascorbic acid-impregnated gelatin hydrogel; Group C, control; Group G, saline-impregnated gelatin hydrogel. B, Dilatation ratio (%) at 4 and 8 weeks. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 3 Histologic findings of abdominal aorta cross-sections at 4 weeks after staining with hematoxylin eosin (H&E) and elastic van Gieson (EVG) for the morphologic assessment and with picrosirius red (PSR) for the collagen content assessment. The upper rows are at the original magnification (×40; bar, 300 μm), and the lower panels are at the original magnification (×400; bar, 100 μm). Group A, Ascorbic acid-impregnated gelatin hydrogel; Group C, control; Group G, saline-impregnated gelatin hydrogel; Native, normal rats. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 4 The quantification of elastin (A) and collagen (B) at 4 weeks. All of the data are expressed as the mean ± standard deviation for six rats in each group. Group A, Ascorbic acid-impregnated gelatin hydrogel; Group C, control; Group G, saline-impregnated gelatin hydrogel; Native, normal rats; NS, not significant. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 5 The assessment of oxidative stress in the aortic wall at day 7. A, Abdominal aorta cross-sections at 1 week after staining with dihydroethidium (DHE) for the in situ imaging of superoxide levels and 8-hydroxydeoxyguanosine (8-OHdG) staining for the assessment of oxidative DNA damage. Group A, Ascorbic acid-impregnated gelatin hydrogel; Group C, control; Group G, saline-impregnated gelatin hydrogel; Native, normal rats; Star, inner aortic lumen. B, The DHE count was semiquantified and expressed relative to values that were obtained for native rats. All of the data are expressed as the mean ± standard deviation for six rats (average of randomly selected five fields) in each group. C, 8-OHdG-positive cell count in a 500- by 380-μm rectangle of the aortic wall. All of the data are expressed as the mean ± standard deviation for six rats (average of randomly selected five fields) in each group. NS, Not significant. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 6 A, Messenger RNA (mRNA) expression of matrix metalloproteinase (MMP), given as a ratio of glyceraldehyde-3-phosphatedehydrogenase (GAPDH) expression in the abdominal aorta at 1 week. All of the data are expressed as the mean ± standard deviation for six rats in each group. Group A, Ascorbic acid-impregnated gelatin hydrogel; Group C, control; Group G, saline-impregnated gelatin hydrogel; NS, nonsignificant; TIMP, tissue inhibitor of metalloproteinase. B, Gelatin zymography documents gelatinolytic activities of pro-MMP-2, MMP-2 and MMP-9. C, Densitometric analysis of MMP activities. *P < .05, **P < .01, ***P < .001. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 7 A, Messenger RNA (mRNA) expressions of inflammatory cytokines, given as a ratio of glyceraldehyde-3-phosphatedehydrogenase (GAPDH) expression in the abdominal aorta at 1 week. All of the data are expressed as the mean ± standard deviation for six rats in each group. Group A, Ascorbic acid-impregnated gelatin hydrogel; Group C, control; Group G, saline-impregnated gelatin hydrogel; IL-1β, interleukin-1 beta; NS, not significant; TNF-α, tissue necrosis factor-alpha. B, Cluster differentiation (CD)68-positive cell count in a 500- by 380-μm rectangle of the aortic wall. All of the data are expressed as the mean ± standard deviation for six rats (average of randomly selected five fields) in each group. C, CD68 and monocyte chemotactic protein (MCP)-1 staining for assessment of macrophage recruitment. *P < .05, **P < .01, ***P < .001. Journal of Vascular Surgery 2014 60, 749-758DOI: (10.1016/j.jvs.2013.07.013) Copyright © 2014 Society for Vascular Surgery Terms and Conditions