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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.

Original publication

DOI

10.1371/journal.pone.0109325

Type

Journal article

Journal

PLoS One

Publication Date

2014

Volume

9

Keywords

Amino Acyl-tRNA Synthetases, Animals, Apoptosis, Biological Products, Capillaries, Cell Proliferation, Fibroblasts, Fibrosis, Heart, Male, Mice, Mice, Inbred C57BL, Myocardial Infarction, Neovascularization, Physiologic, Peptide Fragments, Proto-Oncogene Proteins c-kit