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

Publication ,  Journal Article
Li, W; Shenkar, R; Detter, MR; Moore, T; Benavides, C; Lightle, R; Girard, R; Hobson, N; Cao, Y; Li, Y; Griffin, E; Gallione, C; Ginsberg, MH ...
Published in: J Clin Invest
February 1, 2021

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 1, 2021

Volume

131

Issue

3

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Receptors, Adrenergic, beta-2
  • Proto-Oncogene Proteins
  • Propranolol
  • Programmed Cell Death 1 Receptor
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, W., Shenkar, R., Detter, M. R., Moore, T., Benavides, C., Lightle, R., … Awad, I. A. (2021). Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models. J Clin Invest, 131(3). https://doi.org/10.1172/JCI144893
Li, Wenqing, Robert Shenkar, Mathew R. Detter, Thomas Moore, Christian Benavides, Rhonda Lightle, Romuald Girard, et al. “Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models.J Clin Invest 131, no. 3 (February 1, 2021). https://doi.org/10.1172/JCI144893.
Li W, Shenkar R, Detter MR, Moore T, Benavides C, Lightle R, et al. Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models. J Clin Invest. 2021 Feb 1;131(3).
Li, Wenqing, et al. “Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models.J Clin Invest, vol. 131, no. 3, Feb. 2021. Pubmed, doi:10.1172/JCI144893.
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. Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models. J Clin Invest. 2021 Feb 1;131(3).

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 1, 2021

Volume

131

Issue

3

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Receptors, Adrenergic, beta-2
  • Proto-Oncogene Proteins
  • Propranolol
  • Programmed Cell Death 1 Receptor
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • Male