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.

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.

• Authors: Zipeng Li, Hidetoshi Masumoto, Jun-Ichiro Jo, Kazuhiro Yamazaki, Tadashi Ikeda, Yasuhiko Tabata, Kenji Minatoya
• Journal: General thoracic and cardiovascular surgery (Gen Thorac Cardiovasc Surg) Vol. 66 Issue 11 Pg. 641-647 (Nov 2018) ISSN: 1863-6713 [Electronic] Japan
• PMID: 29982930 (Publication Type: Journal Article)

Chemical References

• Delayed-Action Preparations
• Drug Carriers
• Hydrogels
• Fibroblast Growth Factor 2
• Gelatin
• Collagen

Topics

• Animals
• Cicatrix
• Collagen (metabolism)
• Coronary Vessels (pathology)
• Delayed-Action Preparations
• Disease Models, Animal
• Drug Carriers
• Fibroblast Growth Factor 2 (therapeutic use)
• Gelatin
• Hydrogels
• Male
• Myocardial Infarction (drug therapy, metabolism, physiopathology)
• Myocardial Ischemia (drug therapy, physiopathology)
• Neovascularization, Pathologic
• Rats
• Rats, Inbred F344
• Ventricular Function, Left (drug effects, physiology)