
β1 아드레날린 수용체 억제는 제브라피시에서 태아기 및 성체 뇌혈관 해면상 기형 발생을 현저히 감소시킨다.


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Propranolol reduces experimental murine cerebral cavernous malformations (CCMs) and prevents embryonic caudal venous plexus (CVP) lesions in zebrafish that follow mosaic inactivation of ccm2 . Because morpholino silencing of the β1 adrenergic receptor ( adrb1 ) prevents the embryonic CVP lesion, we proposed that adrb1 plays a role in CCM pathogenesis. Here we report that adrb1-/- zebrafish exhibited 86% fewer CVP lesions and 87% reduction of CCM lesion volume relative to wild type brood mates at 2dpf and 8-10 weeks stage, respectively. Treatment with metoprolol, a β1 selective antagonist, yielded a similar reduction in CCM lesion volume. Adrb1-/- zebrafish embryos exhibited reduced heart rate and contractility and reduced CVP blood flow. Similarly, slowing the heart and eliminating the blood flow in CVP by administration of 2,3-BDM suppressed the CVP lesion. In sum, our findings provide genetic and pharmacological evidence that the therapeutic effect of propranolol on CCM is achieved through β1 receptor antagonism.

### Competing Interest Statement

The authors have declared no competing interest.

Genetic Inactivation of the β1 adrenergic receptor prevents Cerebral Cavernous Malformations in zebrafish

유전자-불활성화를-통한-β1-아드레날린-수용체-억제가-제브라피시에서-뇌혈관-해면상-기형-발생을-예방한다


유전자 불활성화를 통한 β1 아드레날린 수용체 억제가 제브라피시에서 뇌혈관 해면상 기형 발생을 예방한다
