Interaction between Mas1 and AT1RA contributes to enhancement of skeletal muscle angiogenesis by angiotensin-(1-7) in Dahl salt-sensitive rats
| Autor: | Andrew S. Greene, Julian H. Lombard, Timothy J. Stodola, Michael T. Zimmermann, Brian R. Hoffmann, Nikita R. Dsouza, Aron M. Geurts, Eric C. Exner, Marc Casati |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Proteomics Knockout rat Angiogenesis Physiology Peptide Hormones Blood Pressure 030204 cardiovascular system & hematology Cardiovascular Physiology Proto-Oncogene Mas Biochemistry Vascular Medicine Mass Spectrometry Epithelium Receptors G-Protein-Coupled Renin-Angiotensin System Database and Informatics Methods 0302 clinical medicine Animal Cells Medicine and Health Sciences Receptor Tube formation Multidisciplinary Chemistry Proteomic Databases Cell biology Endothelial stem cell medicine.anatomical_structure Models Animal cardiovascular system Medicine Signal transduction Cellular Types Anatomy Cellular Structures and Organelles hormones hormone substitutes and hormone antagonists Signal Transduction Research Article Science Neovascularization Physiologic Surgical and Invasive Medical Procedures Signaling Complexes Research and Analysis Methods Receptor Angiotensin Type 1 03 medical and health sciences Proto-Oncogene Proteins medicine Animals Muscle Skeletal Rats Inbred Dahl Functional Electrical Stimulation Skeletal muscle Biology and Life Sciences Endothelial Cells Proteins Protein Complexes Epithelial Cells Cell Biology Angiotensin II Electric Stimulation Peptide Fragments Hormones Rats 030104 developmental biology Biological Tissue Biological Databases Cell Signaling Structures Mutation Angiotensin I Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 4, p e0232067 (2020) |
| ISSN: | 1932-6203 |
| Popis: | The heptapeptide angiotensin-(1-7) (Ang-(1-7)) is protective in the cardiovascular system through its induction of vasodilator production and angiogenesis. Despite acting antagonistically to the effects of elevated, pathophysiological levels of angiotensin II (AngII), recent evidence has identified convergent and beneficial effects of low levels of both Ang-(1-7) and AngII. Previous work identified the AngII receptor type I (AT1R) as a component of the protein complex formed when Ang-(1-7) binds its receptor, Mas1. Importantly, pharmacological blockade of AT1R did not alter the effects of Ang-(1-7). Here, we use a novel mutation of AT1RA in the Dahl salt-sensitive (SS) rat to test the hypothesis that interaction between Mas1 and AT1R contributes to proangiogenic Ang-(1-7) signaling. In a model of hind limb angiogenesis induced by electrical stimulation, we find that the restoration of skeletal muscle angiogenesis in SS rats by Ang-(1-7) infusion is impaired in AT1RA knockout rats. Enhancement of endothelial cell (EC) tube formation capacity by Ang-(1-7) is similarly blunted in AT1RA mutant ECs. Transcriptional changes elicited by Ang-(1-7) in SS rat ECs are altered in AT1RA mutant ECs, and tandem mass spectrometry-based proteomics demonstrate that the protein complex formed upon binding of Ang-(1-7) to Mas1 is altered in AT1RA mutant ECs. Together, these data support the hypothesis that interaction between AT1R and Mas1 contributes to proangiogenic Ang-(1-7) signaling. |
| Databáze: | OpenAIRE |
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