title: Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction.
abstract: 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.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: McCormick
authors.affiliation: UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Tyler
authors.initials: T
authors.lastname: Moser-Katz
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Ellie
authors.initials: E
authors.lastname: Tzima
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Reader
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
chemical_list: D001688:Biological Products; D010446:Peptide Fragments; D019009:Proto-Oncogene Proteins c-kit; D000604:Amino Acyl-tRNA Synthetases