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Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model

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Abstract

Objective

Chronic myocardial infarction (CMI) tends to be resistant to treatments possibly due to extensive solid fibrotic scar, hypoxia mediated by poorly vascularized environment, and/or inflammation and apoptosis. Here we aimed to testify the therapeutic effects of sustained release of basic fibroblast growth factor (bFGF) using gelatin hydrogel (GH) in a rat chronic MI model and to elucidate the therapeutic mechanism including the alteration of extracellular matrix component.

Methods

CMI model rats are prepared by the permanent ligation of proximal left anterior descending coronary artery. After 4 weeks, GH sheets (GHSs) with bFGF (100 µg) (bFGF group) or with phosphate-buffered saline (Vehicle group) were implanted to the CMI models to evaluate the effect of bFGF–GHS on chronic scar tissue. Sham operation group was also prepared (n = 5 for each).

Results

4 weeks after implantation, bFGF–GHS significantly improved cardiac contractile function (fractional shortening: 21.8 ± 1.1 vs 21.5 ± 1.3 vs 29.7 ± 1.8%; P < 0.001/fractional area change: 33.0 ± 1.4 vs 34.1 ± 2.3 vs 40.6 ± 1.8%; P < 0.001) (Sham vs Vehicle vs bFGF) accompanied with neovascularization. Immunohistochemical studies revealed that bFGF–GHS increased collagen III/I ratio indicating the alteration of solid scar tissue. Quantitative RT-PCR results showed a decrease of collagen I mRNA expression within border MI zone.

Conclusions

The implantation of bFGF–GHS altered the collagen subtype of the fibrotic scar more suitable for tissue repair. The treatment of sustained-release bFGF may be promising for ischemic heart disease through chronic pathology.

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Acknowledgements

This work was supported by grants from Japan Agency for Medical Research and development (AMED) (to KM), and Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to HM) (#25462137). We thank Shuichi Miyake (Kyoto Univ.) for the excellent technical support.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Zipeng Li, Hidetoshi Masumoto, Kazuhiro Yamazaki, Tadashi Ikeda & Kenji Minatoya

  2. Department of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan

    Jun-ichiro Jo & Yasuhiko Tabata

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  1. Zipeng Li
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  2. Hidetoshi Masumoto
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  4. Kazuhiro Yamazaki
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Correspondence to Hidetoshi Masumoto.

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Li, Z., Masumoto, H., Jo, Ji. et al. Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model. Gen Thorac Cardiovasc Surg 66, 641–647 (2018). https://doi.org/10.1007/s11748-018-0969-z

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