Wars2 is a determinant of angiogenesis
| Autor: | Brittney Mikell, Sebastian Schafer, Permeen Yusoff, Michal Pravenec, Anissa A. Widjaja, David M. Epstein, Stuart A. Cook, Hana Nuskova, Jessie Tan, Pervinder Kaur Choksi, Nicole S. J. Ko, Frantisek Kolar, Massimiliano Mancini, Ester Khin, Enrico Petretto, Leonardo Bottolo, Xi-Ming Sun, Norbert Hubner, Rizwan Ahmed, Calum A. MacRae, Tomáš Mráček, Patrick Sips, Josef Houštěk, Yuguang Guan, Francesco Pesce, Mao Wang, Manvendra K. Singh, Maxime Rotival |
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| Přispěvatelé: | Sips, Patrick [0000-0001-9241-5980], Pesce, Francesco [0000-0002-2882-4226], Bottolo, Leonardo [0000-0002-6381-2327], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
BLOOD Embryo Nonmammalian Angiogenesis General Physics and Astronomy Tryptophan-tRNA Ligase 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit Neovascularization RNA Small Interfering CARDIAC-HYPERTROPHY Zebrafish Multidisciplinary Genome Chromosome Mapping Gene Expression Regulation Developmental Cell biology Mitochondria DEFICIENCY cardiovascular system HEART-FAILURE GROWTH medicine.symptom Signal Transduction medicine.medical_specialty Science Neovascularization Physiologic Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Spontaneously hypertensive rat Medical research In vivo Internal medicine REVEALS MD Multidisciplinary medicine Human Umbilical Vein Endothelial Cells Animals Humans Amino Acid Sequence TRANSFER-RNA-SYNTHETASE Sequence Homology Amino Acid ZEBRAFISH Myocardium HEK 293 cells Biology and Life Sciences General Chemistry Cardiovascular genetics medicine.disease biology.organism_classification Chromosomes Mammalian SPONTANEOUSLY HYPERTENSIVE-RAT Rats 030104 developmental biology Endocrinology HEK293 Cells CORONARY VASCULATURE Cardiovascular and Metabolic Diseases Genetic Loci Heart failure Sequence Alignment Ex vivo |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016) Nature Communications NATURE COMMUNICATIONS |
| ISSN: | 2041-1723 |
| Popis: | Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases. Blood supply to the heart is crucial for cardiac function. Here, the authors show that the mitochondrial tryptophanyl-tRNA synthetase, WARS2, drives blood vessel generation in zebrafish and rats and that inhibition of Wars2 diminishes blood vessel growth both within and outside in the heart, suggesting a new target for manipulating angiogenesis. |
| Databáze: | OpenAIRE |
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