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Propranolol inhibits cavernous vascular malformations by β1 adrenergic receptor antagonism in animal models
Wenqing Li, Robert Shenkar, Mathew R. Detter, Thomas Moore, Christian Benavides, Rhonda Lightle, Romuald Girard, Nicholas Hobson, Ying Cao, Yan Li, Erin Griffin, Carol Gallione, Joseph M. Zabramski, Mark H. Ginsberg, Douglas A. Marchuk, and Issam A. Awad
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Published October 1, 2021 - More info
J Clin Invest. 2021;131(19):e154909. https://doi.org/10.1172/JCI154909.
© 2021 American Society for Clinical Investigation
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Abstract
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.
Authors
Wenqing Li, Robert Shenkar, Mathew R. Detter, Thomas Moore, Christian Benavides, Rhonda Lightle, Romuald Girard, Nicholas Hobson, Ying Cao, Yan Li, Erin Griffin, Carol Gallione, Joseph M. Zabramski, Mark H. Ginsberg, Douglas A. Marchuk, Issam A. Awad
Original citation: J Clin Invest. 2021;131(3):e144893. https://doi.org/10.1172/JCI144893
Citation for this corrigendum: J Clin Invest. 2021;131(19):e154909. https://doi.org/10.1172/JCI154909
Following the publication of this article, the authors became aware that an incorrect panel was used for Figure 3B. The correct panel for Figure 3B is below, showing the change in heart rate when mice were challenged with isoproterenol in a murine model of cerebral cavernous malformation treated with vehicle or propranolol. The Figure 3 legend is amended as follows: ***P < 0.001, by 2-way repeated-measures ANOVA with a post hoc Tukey’s honest significant difference test. The authors have stated that this corrected panel does not affect the results or conclusions of the article.
The authors regret the error.
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)