Endothelial EphB4 maintains vascular integrity and transport function in adult heart
The homeostasis of heart and other organs relies on the appropriate provision of nutrients and functional specialization of the local vasculature. Here, we have used mouse genetics, imaging and cell biology approaches to investigate how homeostasis in the adult heart is controlled by endothelial Eph...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/45863 |
| _version_ | 1811236907989860352 |
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| author | Guillermo Luxán Jonas Stewen Noelia Díaz Katsuhiro Kato Sathish K Maney Anusha Aravamudhan Frank Berkenfeld Nina Nagelmann Hannes CA Drexler Dagmar Zeuschner Cornelius Faber Hermann Schillers Sven Hermann John Wiseman Juan M Vaquerizas Mara E Pitulescu Ralf H Adams |
| author_facet | Guillermo Luxán Jonas Stewen Noelia Díaz Katsuhiro Kato Sathish K Maney Anusha Aravamudhan Frank Berkenfeld Nina Nagelmann Hannes CA Drexler Dagmar Zeuschner Cornelius Faber Hermann Schillers Sven Hermann John Wiseman Juan M Vaquerizas Mara E Pitulescu Ralf H Adams |
| author_sort | Guillermo Luxán |
| collection | DOAJ |
| description | The homeostasis of heart and other organs relies on the appropriate provision of nutrients and functional specialization of the local vasculature. Here, we have used mouse genetics, imaging and cell biology approaches to investigate how homeostasis in the adult heart is controlled by endothelial EphB4 and its ligand ephrin-B2, which are known regulators of vascular morphogenesis and arteriovenous differentiation during development. We show that inducible and endothelial cell-specific inactivation of Ephb4 in adult mice is compatible with survival, but leads to rupturing of cardiac capillaries, cardiomyocyte hypertrophy, and pathological cardiac remodeling. In contrast, EphB4 is not required for integrity and homeostasis of capillaries in skeletal muscle. Our analysis of mutant mice and cultured endothelial cells shows that EphB4 controls the function of caveolae, cell-cell adhesion under mechanical stress and lipid transport. We propose that EphB4 maintains critical functional properties of the adult cardiac vasculature and thereby prevents dilated cardiomyopathy-like defects. |
| first_indexed | 2024-04-12T12:17:18Z |
| format | Article |
| id | doaj.art-e3991c813b8a40cf85e25a8c9c3f9f01 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:17:18Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e3991c813b8a40cf85e25a8c9c3f9f012022-12-22T03:33:24ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.45863Endothelial EphB4 maintains vascular integrity and transport function in adult heartGuillermo Luxán0https://orcid.org/0000-0001-8350-8659Jonas Stewen1Noelia Díaz2https://orcid.org/0000-0002-0319-3448Katsuhiro Kato3Sathish K Maney4Anusha Aravamudhan5Frank Berkenfeld6Nina Nagelmann7Hannes CA Drexler8Dagmar Zeuschner9Cornelius Faber10https://orcid.org/0000-0001-7683-7710Hermann Schillers11Sven Hermann12John Wiseman13Juan M Vaquerizas14https://orcid.org/0000-0002-6583-6541Mara E Pitulescu15Ralf H Adams16https://orcid.org/0000-0003-3031-7677Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyRegulatory Genomics Laboratory, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Clinical Radiology, University Hospital Münster, Münster, GermanyBioanalytical Mass Spectrometry Unit, Max Planck Institute for Molecular Biomedicine, Münster, GermanyElectron Microscopy Unit, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Clinical Radiology, University Hospital Münster, Münster, GermanyInstitute for Physiology II, University of Münster, Münster, GermanyEuropean Institute for Molecular Imaging, University of Münster, Münster, GermanyDiscovery Biology, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, SwedenRegulatory Genomics Laboratory, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, GermanyDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany; Faculty of Medicine, University of Münster, Münster, GermanyThe homeostasis of heart and other organs relies on the appropriate provision of nutrients and functional specialization of the local vasculature. Here, we have used mouse genetics, imaging and cell biology approaches to investigate how homeostasis in the adult heart is controlled by endothelial EphB4 and its ligand ephrin-B2, which are known regulators of vascular morphogenesis and arteriovenous differentiation during development. We show that inducible and endothelial cell-specific inactivation of Ephb4 in adult mice is compatible with survival, but leads to rupturing of cardiac capillaries, cardiomyocyte hypertrophy, and pathological cardiac remodeling. In contrast, EphB4 is not required for integrity and homeostasis of capillaries in skeletal muscle. Our analysis of mutant mice and cultured endothelial cells shows that EphB4 controls the function of caveolae, cell-cell adhesion under mechanical stress and lipid transport. We propose that EphB4 maintains critical functional properties of the adult cardiac vasculature and thereby prevents dilated cardiomyopathy-like defects.https://elifesciences.org/articles/45863heartblood vesselhomeostasiscardiomyocyteendothelial cell |
| spellingShingle | Guillermo Luxán Jonas Stewen Noelia Díaz Katsuhiro Kato Sathish K Maney Anusha Aravamudhan Frank Berkenfeld Nina Nagelmann Hannes CA Drexler Dagmar Zeuschner Cornelius Faber Hermann Schillers Sven Hermann John Wiseman Juan M Vaquerizas Mara E Pitulescu Ralf H Adams Endothelial EphB4 maintains vascular integrity and transport function in adult heart eLife heart blood vessel homeostasis cardiomyocyte endothelial cell |
| title | Endothelial EphB4 maintains vascular integrity and transport function in adult heart |
| title_full | Endothelial EphB4 maintains vascular integrity and transport function in adult heart |
| title_fullStr | Endothelial EphB4 maintains vascular integrity and transport function in adult heart |
| title_full_unstemmed | Endothelial EphB4 maintains vascular integrity and transport function in adult heart |
| title_short | Endothelial EphB4 maintains vascular integrity and transport function in adult heart |
| title_sort | endothelial ephb4 maintains vascular integrity and transport function in adult heart |
| topic | heart blood vessel homeostasis cardiomyocyte endothelial cell |
| url | https://elifesciences.org/articles/45863 |
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