Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability
| Autor: | Eleni Tzima, Karla L. Ewalt, Hua Zhang, Paul Schimmel, James E. Faber, Xiang-Lei Yang, Gang Cheng |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
Physiology Angiogenesis medicine.medical_treatment Ischemia Neovascularization Physiologic Aorta Thoracic Mice Inbred Strains Vascular permeability Biology Capillary Permeability Mice chemistry.chemical_compound Cell Movement Tyrosine-tRNA Ligase Physiology (medical) Leukocytes medicine Animals Humans Hemodynamics and Cardiorenal Integration Ear External Hypoxia Muscle Skeletal Ligation Arteries medicine.disease Peptide Fragments In vitro Capillaries Rats Cell biology Femoral Artery Mice Inbred C57BL Endothelial stem cell Vascular endothelial growth factor Cytokine medicine.anatomical_structure chemistry Regional Blood Flow Vasoconstriction Immunology Cattle Blood vessel |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 295:R1138-R1146 |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Mini-tyrosyl-tRNA synthetase (mini-TyrRS), the N-terminal domain of tyrosyl-tRNA synthetase, is a recently identified protein released by endothelial cells that exhibits angiogenic and leukocyte chemoattractant, ELR-motif (Glu-Leu-Arg)-dependent activities in vitro. We sought to determine whether exogenous mini-TyrRS exerts these and other cytokine-like actions in physiological and pathological settings in vivo. High-dose mini-TyrRS (600 μg·kg−1·day−1) augmented while low-dose mini-TyrRS (3 μg·kg−1·day−1), unexpectedly, inhibited angiogenesis in the ischemic mouse ear. Enhanced angiogenesis was associated with increased CD45- and CD4-positive leukocyte accumulation. Mini-TyrRS also had biphasic actions on both basal and mustard oil-evoked and VEGF-evoked leakage of Evan's blue dye-albumin in nonischemic ear and in endothelial cell monolayers, that is, low-dose inhibited and high-dose augmented leakage. Mutation of the ELR motif of mini-TyrRS abolished the above activities. Mini-TyrRS was reduced (immunoblot) in extracts of ischemic calf muscle and in thoracic aorta explants exposed to hypoxia or VEGF. Inhibition of VEGF with a soluble Flt1 “trap” protein abolished this hypoxic-induced reduction in mini-TyrRS in aorta explants. These data show that mini-TyrRS has dose-dependent biphasic effects on ischemic angiogenesis and vascular permeability in vivo, that is, antiangiogenic and antipermeability activities at low concentration and proangiogenic, propermeability activities at high concentrations. |
| Databáze: | OpenAIRE |
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