Zipeng Li1, Hidetoshi Masumoto2, Jun-Ichiro Jo3, Kazuhiro Yamazaki1, Tadashi Ikeda1, Yasuhiko Tabata3, Kenji Minatoya1. 1. Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. 2. Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. masumoto@kuhp.kyoto-u.ac.jp. 3. Department of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
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.
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.
Authors: Emerson C Perin; James T Willerson; Carl J Pepine; Timothy D Henry; Stephen G Ellis; David X M Zhao; Guilherme V Silva; Dejian Lai; James D Thomas; Marvin W Kronenberg; A Daniel Martin; R David Anderson; Jay H Traverse; Marc S Penn; Saif Anwaruddin; Antonis K Hatzopoulos; Adrian P Gee; Doris A Taylor; Christopher R Cogle; Deirdre Smith; Lynette Westbrook; James Chen; Eileen Handberg; Rachel E Olson; Carrie Geither; Sherry Bowman; Judy Francescon; Sarah Baraniuk; Linda B Piller; Lara M Simpson; Catalin Loghin; David Aguilar; Sara Richman; Claudia Zierold; Judy Bettencourt; Shelly L Sayre; Rachel W Vojvodic; Sonia I Skarlatos; David J Gordon; Ray F Ebert; Minjung Kwak; Lemuel A Moyé; Robert D Simari Journal: JAMA Date: 2012-03-24 Impact factor: 56.272
Authors: Angela M Gutierrez; Erin Molly Frazar; Maria Victoria X Klaus; Pranto Paul; J Zach Hilt Journal: Adv Healthc Mater Date: 2021-12-11 Impact factor: 9.933