PUBLICATION

Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations

Authors
Rödel, C.J., Otten, C., Donat, S., Lourenco, M., Fischer, D., Kuropka, B., Paolini, A., Freund, C., Abdelilah-Seyfried, S.
ID
ZDB-PUB-190910-1
Date
2019
Source
Circulation research   125(10): e43-e54 (Journal)
Registered Authors
Abdelilah-Seyfried, Salim, Paolini, Alessio
Keywords
CCM, KLF2, KLF4, cerebral blood flow, stroke
MeSH Terms
  • Animals
  • 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
  • Zebrafish
PubMed
31495257 Full text @ Circ. Res.
Abstract
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.
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.
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.
This study identifies blood flow as an important physiological factor that is protective in the etiology of this devastating vascular pathology.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes