Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations
- Rödel, C.J., Otten, C., Donat, S., Lourenco, M., Fischer, D., Kuropka, B., Paolini, A., Freund, C., Abdelilah-Seyfried, S.
- Circulation research 125(10): e43-e54 (Journal)
- Registered Authors
- Abdelilah-Seyfried, Salim, Paolini, Alessio
- CCM, KLF2, KLF4, cerebral blood flow, stroke
- MeSH Terms
- Animals, Genetically Modified
- Blood Flow Velocity/physiology*
- Central Nervous System Neoplasms/diagnostic imaging*
- Central Nervous System Neoplasms/physiopathology
- Cerebral Angiography/methods
- Disease Models, Animal*
- Hemangioma, Cavernous, Central Nervous System/diagnostic imaging*
- Hemangioma, Cavernous, Central Nervous System/physiopathology
- 31495257 Full text @ Circ. Res.
Rödel, C.J., Otten, C., Donat, S., Lourenco, M., Fischer, D., Kuropka, B., Paolini, A., Freund, C., Abdelilah-Seyfried, S. (2019) Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations. Circulation research. 125(10):e43-e54.
Rationale Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1, 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 etiology of this devastating vascular pathology.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes