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

Overview

Journal Gen Thorac Cardiovasc Surg

Specialties Cardiology & Vascular Diseases
General Surgery
Pulmonary Medicine

Date 2018 Jul 9

PMID 29982930

Citations 15

Authors

Zipeng Li

Hidetoshi Masumoto

Jun-Ichiro Jo

Kazuhiro Yamazaki

Tadashi Ikeda

Yasuhiko Tabata

Kenji Minatoya

Affiliations

Soon will be listed here.

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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