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Natural Aminoacyl tRNA Synthetase Fragment Enhances Cardiac Function after Myocardial Infarction
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Natural Aminoacyl tRNA Synthetase Fragment Enhances Cardiac Function after Myocardial Infarction
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Journal Article
Natural Aminoacyl tRNA Synthetase Fragment Enhances Cardiac Function after Myocardial Infarction
2014
Overview
A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS) has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Amino Acyl-tRNA Synthetases - chemistry
/ Animals
/ Biological Products - pharmacology
/ Biological Products - therapeutic use
/ Biology
/ Capillaries - physiopathology
/ Cell Proliferation - drug effects
/ Fibrosis
/ Heart
/ Ischemia
/ Male
/ Medicine and Health Sciences
/ Mice
/ Myocardial Infarction - drug therapy
/ Myocardial Infarction - pathology
/ Myocardial Infarction - physiopathology
/ Neovascularization, Physiologic - drug effects
/ Ostomy
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Peptide Fragments - therapeutic use
/ Proto-Oncogene Proteins c-kit - metabolism
/ Rodents
/ tRNA
