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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説明
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.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).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.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.
収録刊行物
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- General Thoracic and Cardiovascular Surgery
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General Thoracic and Cardiovascular Surgery 66 (11), 641-647, 2018-07-07
Springer Science and Business Media LLC
