A novel fibroblast growth factor-1 ligand with reduced heparin binding protects the heart against ischemia-reperfusion injury in the presence of heparin co-administration

Fibroblast growth factor 1 (FGF1), a heparin/heparan sulfate-binding growth factor, is a potent cardioprotective agent against myocardial infarction (MI). The impact of heparin, the standard of care for MI patients entering the emergency room, on cardioprotective effects of FGF1 is unknown, however....

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Bibliographic Details
Published in:	Cardiovascular research 2017-11, Vol.113 (13), p.1585-1602
Main Authors:	Huang, Chahua, Liu, Yang, Beenken, Andrew, Jiang, Lin, Gao, Xiang, Huang, Zhifeng, Hsu, Anna, Gross, Garrett J, Wang, Yi-Gang, Mohammadi, Moosa, Schultz, Jo El J
Format:	Article
Language:	eng
Subjects:	Animals Cardiovascular Agents - metabolism Cardiovascular Agents - pharmacokinetics Cardiovascular Agents - pharmacology Disease Models, Animal Extracellular Signal-Regulated MAP Kinases - metabolism Fibroblast Growth Factor 1 - genetics Fibroblast Growth Factor 1 - metabolism Fibroblast Growth Factor 1 - pharmacokinetics Fibroblast Growth Factor 1 - pharmacology Heparin - metabolism Heparin - pharmacology Humans Ligands Male Mutation Myocardial Contraction - drug effects Myocardial Infarction - metabolism Myocardial Infarction - pathology Myocardial Infarction - physiopathology Myocardial Infarction - prevention & control Myocardial Reperfusion Injury - metabolism Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - physiopathology Myocardial Reperfusion Injury - prevention & control Myocardium - metabolism Myocardium - pathology Original Protein Binding Rats, Sprague-Dawley Receptor, Fibroblast Growth Factor, Type 1 - metabolism Recovery of Function Tissue Distribution Ventricular Function, Left - drug effects
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Summary:	Fibroblast growth factor 1 (FGF1), a heparin/heparan sulfate-binding growth factor, is a potent cardioprotective agent against myocardial infarction (MI). The impact of heparin, the standard of care for MI patients entering the emergency room, on cardioprotective effects of FGF1 is unknown, however. To address this, a rat model of MI was employed to compare cardioprotective potentials (lower infarct size and improve post-ischemic function) of native FGF1 and an engineered FGF1 (FGF1ΔHBS) with reduced heparin-binding affinity when given at the onset of reperfusion in the absence or presence of heparin. FGF1 and FGF1ΔHBS did not alter heparin's anticoagulant properties. Treatment with heparin alone or native FGF1 significantly reduced infarct size compared to saline (P
ISSN:	0008-6363 1755-3245