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

Abstract

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 is protective in the cause of this devastating vascular pathology.

• Authors: Claudia Jasmin Rödel, Cécile Otten, Stefan Donat, Marta Lourenço, Dorothea Fischer, Benno Kuropka, Alessio Paolini, Christian Freund, Salim Abdelilah-Seyfried
• Journal: Circulation research (Circ Res) Vol. 125 Issue 10 Pg. e43-e54 (10 25 2019) ISSN: 1524-4571 [Electronic] United States
• PMID: 31495257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Animals, Genetically Modified
• Blood Flow Velocity (physiology)
• Central Nervous System Neoplasms (diagnostic imaging, physiopathology)
• Cerebral Angiography (methods)
• Disease Models, Animal
• Hemangioma, Cavernous, Central Nervous System (diagnostic imaging, physiopathology)
• Zebrafish