Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models.

Journal Article (Journal Article)

Propranolol, a pleiotropic β-adrenergic blocker, has been anecdotally reported to reduce cerebral cavernous malformations (CCMs) in humans. However, propranolol has not been rigorously evaluated in animal models, nor has its mechanism of action in CCM been defined. We report that propranolol or its S(-) enantiomer dramatically reduced embryonic venous cavernomas in ccm2 mosaic zebrafish, whereas R-(+)-propranolol, lacking β antagonism, had no effect. Silencing of the β1, but not β2, adrenergic receptor mimicked the beneficial effects of propranolol in a zebrafish CCM model, as did the β1-selective antagonist metoprolol. Thus, propranolol ameliorated cavernous malformations by β1 adrenergic antagonism in zebrafish. Oral propranolol significantly reduced lesion burden in 2 chronic murine models of the exceptionally aggressive Pdcd10/Ccm3 form of CCM. Propranolol or other β1-selective antagonists may be beneficial in CCM disease.

Full Text

Duke Authors

Cited Authors

  • Li, W; Shenkar, R; Detter, MR; Moore, T; Benavides, C; Lightle, R; Girard, R; Hobson, N; Cao, Y; Li, Y; Griffin, E; Gallione, C; Zabramski, JM; Ginsberg, MH; Marchuk, DA; Awad, IA

Published Date

  • February 1, 2021

Published In

Volume / Issue

  • 131 / 3

PubMed ID

  • 33301422

Pubmed Central ID

  • PMC7843213

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI144893

Language

  • eng

Conference Location

  • United States