Raw images from: Genetic inactivation of the β1 adrenergic receptor prevents Cerebral Cavernous Malformations in zebrafish

Propranolol reduces experimental murine Cerebral Cavernous Malformations
(CCMs) and prevents embryonic caudal venous plexus (CVP) lesions in
zebrafish that follow mosaic inactivation of ccm2(Li et al., 2021).
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.