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Suppression of aortic expansion and contractile recovery in a rat abdominal aortic aneurysm model by biodegradable gelatin hydrogel sheet incorporating basic fibroblast growth factor

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Abstract

Biodegradable gelatin hydrogel sheet (BGHS) incorporating basic fibroblast growth factor (bFGF) may inhibit the progression of abdominal aortic aneurysm (AAA). We investigated whether AAA in a rat model treated with BGHS soaked with bFGF can suppress aortic expansion and recover the contractile response of aneurysmal aortic wall. Experimental AAA was induced in 10-week-old male Sprague–Dawley rats with intra-aortic elastase infusion. Aortas of these rats were assigned to 4 groups (n = 6 each) as follows: Control group, aortas infused with saline; Elastase only group, aortas infused with elastase; Hydrogel group, aortas wrapped with saline-soaked BGHS after elastase infusion; and bFGF group, aortas wrapped with bFGF (100 μg)-soaked BGHS after elastase infusion. Preoperatively and on postoperative day (POD)7 and POD14, mean aortic maximal diameter was measured ultrasonographically. Aortic expansion ratio was calculated as: (post-infusion aortic diameter on POD14/pre-infusion aortic diameter × 100). Aortas were stained with Elastica van Gieson and α-smooth muscle actin to measure the ratio of elastic fibers and α-smooth muscle actin-positive cells area to the media area. Aortas on POD14 were cut into 2-mm rings and treated with contractile agent, then tension was recorded using myography. Maximum aorta diameters were significantly greater in Elastase only group, Hydrogel group, and bFGF group than in Control group (on POD14). Maximum diameter was significantly lower in bFGF group (3.52 ± 0.4 mm) than in Elastase only group (6.21 ± 1.4 mm on POD14, P < .05). On histological analysis, ratio of the area staining positively for elastic fibers was significantly greater in bFGF group (7.43 ± 1.8%) than in Elastase only group (3.76 ± 2.9%, P < .05). The ratio for α-smooth muscle actin-positive cells was significantly lower in Elastase only group (38.3 ± 5.1%) than in Control group (49.8 ± 6.7%, P < .05). No significant differences were seen between Elastase only group and bFGF group, but ratios tended to be increased in bFGF group. Consecutive mean contractile tensions were significantly higher in bFGF group than in Elastase only group. Maximum contractile tension was significantly higher in bFGF group (1.3 ± 0.4 mN) than in Elastase only group (0.4 ± 0.2 mN, P < .05). Aortic expansion can be suppressed and contractile responses of aneurysmal aortic wall recovered using BGHS incorporating bFGF.

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Acknowledgements

We would like to thank Kaken Pharmaceutical for providing bFGF, and also gratefully acknowledge Ms Yoshimi Hayashi and Tomoko Kamiya for their secretarial support, and Hisato Takagi, MD, PhD, for statistical advice, and we would also like to express our gratitude to the Department of General and Cardiothoracic Surgery, Graduate School of Medicine, Gifu University, for their financial support.

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Authors and Affiliations

  1. Department of General and Cardiothoracic Surgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan

    Norikazu Kawai, Hisashi Iwata, Katsuya Shimabukuro, Narihiro Ishida, Hiroki Ogura, Etsuji Umeda & Kiyoshi Doi

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  1. Norikazu Kawai
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  2. Hisashi Iwata
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  3. Katsuya Shimabukuro
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Correspondence to Hisashi Iwata.

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Kawai, N., Iwata, H., Shimabukuro, K. et al. Suppression of aortic expansion and contractile recovery in a rat abdominal aortic aneurysm model by biodegradable gelatin hydrogel sheet incorporating basic fibroblast growth factor. Heart Vessels 33, 793–801 (2018). https://doi.org/10.1007/s00380-017-1114-0

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  • DOI: https://doi.org/10.1007/s00380-017-1114-0

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