- RATIONALE: Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1 (Krev interaction trapped protein 1), CCM2/MGC4607, or CCM3/PDCD10. Why patients typically experience lesions only in lowly perfused venous capillaries of the cerebrovasculature is completely unknown. OBJECTIVE: In contrast, animal models with a complete loss of CCM proteins lack a functional heart and blood flow and exhibit vascular anomalies within major blood vessels as well. This finding raises the possibility that hemodynamics may play a role in the context of this vascular pathology. METHODS AND RESULTS: Here, we used a genetic approach to restore cardiac function and blood flow in a zebrafish model of CCM1. We find that blood flow prevents cardiovascular anomalies including a hyperplastic expansion within a large Ccm1-deficient vascular bed, the lateral dorsal aorta. CONCLUSIONS: This study identifies blood flow as an important physiological factor that isRATIONALE: Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1 (Krev interaction trapped protein 1), CCM2/MGC4607, or CCM3/PDCD10. Why patients typically experience lesions only in lowly perfused venous capillaries of the cerebrovasculature is completely unknown. OBJECTIVE: In contrast, animal models with a complete loss of CCM proteins lack a functional heart and blood flow and exhibit vascular anomalies within major blood vessels as well. This finding raises the possibility that hemodynamics may play a role in the context of this vascular pathology. METHODS AND RESULTS: Here, we used a genetic approach to restore cardiac function and blood flow in a zebrafish model of CCM1. We find that blood flow prevents cardiovascular anomalies including a hyperplastic expansion within a large Ccm1-deficient vascular bed, the lateral dorsal aorta. CONCLUSIONS: This study identifies blood flow as an important physiological factor that is protective in the cause of this devastating vascular pathology.…
MetadatenVerfasserangaben: | Claudia Jasmin RödelORCiD, Cecile OttenORCiDGND, Stefan DonatORCiDGND, Marta Sofia Rocha LourençoGND, Dorothea Fischer, Benno KuropkaORCiDGND, Alessio PaoliniORCiDGND, Christian FreundORCiDGND, Salim Abdelilah-SeyfriedORCiDGND |
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DOI: | https://doi.org/10.1161/CIRCRESAHA.119.315076 |
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ISSN: | 0009-7330 |
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ISSN: | 1524-4571 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31495257 |
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Titel des übergeordneten Werks (Englisch): | Circulation Research |
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Verlag: | Lippincott Williams & Wilkins |
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Verlagsort: | Philadelphia |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Datum der Erstveröffentlichung: | 09.09.2019 |
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Erscheinungsjahr: | 2019 |
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Datum der Freischaltung: | 25.10.2020 |
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Freies Schlagwort / Tag: | animal models; cerebral cavernous malformations; endothelial cell; hemodynamics; zebrafish |
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Band: | 125 |
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Ausgabe: | 10 |
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Seitenanzahl: | 12 |
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Erste Seite: | E43 |
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Letzte Seite: | E54 |
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Fördernde Institution: | Excellence cluster REBIRTH, SFB958; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [SE2016/7-2, SE2016/10-1]; DZHK |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer Review: | Referiert |
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