Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction
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 mecha...
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| Veröffentlicht in: | PloS one 2014-10, Vol.9 (10), p.e109325-e109325 |
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| creator | McCormick, Margaret E Rojas, Mauricio Moser-Katz, Tyler Tzima, Ellie Reader, John S |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0109325 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0109325</identifier><identifier>PMID: 25296172</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino Acyl-tRNA Synthetases - chemistry ; Angiogenesis ; Animals ; Apoptosis - drug effects ; Biological Products - pharmacology ; Biological Products - therapeutic use ; Biology ; Biology and Life Sciences ; Capillaries ; Capillaries - drug effects ; Capillaries - physiopathology ; Cardiomyocytes ; Cell proliferation ; Cell Proliferation - drug effects ; Coronary vessels ; Cytokines ; Drug development ; Eukaryotes ; Fibroblasts ; Fibroblasts - drug effects ; Fibroblasts - pathology ; Fibrosis ; Fragmentation ; Growth factors ; Heart ; Heart - drug effects ; Heart - physiopathology ; Heart attacks ; Heart diseases ; Heart function ; Ischemia ; Laboratory animals ; Male ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Myocardial infarction ; 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 ; Physiology ; Proto-Oncogene Proteins c-kit - metabolism ; Regeneration ; Rodents ; Stem cells ; tRNA ; Tyrosine-tRNA ligase ; Veins & arteries</subject><ispartof>PloS one, 2014-10, Vol.9 (10), p.e109325-e109325</ispartof><rights>2014 McCormick et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25296172</pmid><doi>10.1371/journal.pone.0109325</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acyl-tRNA Synthetases - chemistry Angiogenesis Animals Apoptosis - drug effects Biological Products - pharmacology Biological Products - therapeutic use Biology Biology and Life Sciences Capillaries Capillaries - drug effects Capillaries - physiopathology Cardiomyocytes Cell proliferation Cell Proliferation - drug effects Coronary vessels Cytokines Drug development Eukaryotes Fibroblasts Fibroblasts - drug effects Fibroblasts - pathology Fibrosis Fragmentation Growth factors Heart Heart - drug effects Heart - physiopathology Heart attacks Heart diseases Heart function Ischemia Laboratory animals Male Medicine and Health Sciences Mice Mice, Inbred C57BL Myocardial infarction 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 Physiology Proto-Oncogene Proteins c-kit - metabolism Regeneration Rodents Stem cells tRNA Tyrosine-tRNA ligase Veins & arteries |
| title | Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction |
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