biostudies-literatureSeebauer CTNational Health and Medical Research Council Career Development FellowsDeutsche Forschungsgemeinschaft (DFG) grantNHLBI NIH HHSNational Health and Medical Research CouncilNational Institutes of Healthe151109https://www.ebi.ac.uk/biostudies/studies/S-EPMC8803322biostudies-literatureUnknown132(3)Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(-) enantiomers: the R(+) enantiomer is largely devoid of beta blocker activity. We investigated the effect of R(+) enantiomers of propranolol and atenolol on the formation of IH-like blood vessels from hemangioma stem cells (HemSCs) in a murine xenograft model. Both R(+) enantiomers inhibited HemSC vessel formation in vivo. In vitro, similar to R(+) propranolol, both atenolol and its R(+) enantiomer inhibited HemSC to endothelial cell differentiation. As our previous work implicated the transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18) in propranolol-mediated inhibition of HemSC to endothelial differentiation, we tested in parallel a known The Journal of clinical investigationNon-beta blocker enantiomers of propranolol and atenolol inhibit vasculogenesis in infantile hemangioma.PMC8803322GNT1111169SE 3066/1-1R01 HL096384GNT1164000HL 096384-09Fontaine FKarnezis TZurakowski DHuang LWylie-Sears JGraus MSMcCann AFrancois MSeebauer CTMeunier FStaffa SJMulliken JBBischoff JfalseNon-beta blocker enantiomers of propranolol and atenolol inhibit vasculogenesis in infantile hemangioma.Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(-) enantiomers: the R(+) enantiomer is largely devoid of beta blocker activity. We investigated the effect of R(+) enantiomers of propranolol and atenolol on the formation of IH-like blood vessels from hemangioma stem cells (HemSCs) in a murine xenograft model. Both R(+) enantiomers inhibited HemSC vessel formation in vivo. In vitro, similar to R(+) propranolol, both atenolol and its R(+) enantiomer inhibited HemSC to endothelial cell differentiation. As our previous work implicated the transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18) in propranolol-mediated inhibition of HemSC to endothelial differentiation, we tested in parallel a known 2022-01-01T00:00:00Z2022 Feb2026-06-18T08:48:34.715Z2025-04-19T13:19:34.336ZS-EPMC88033223487491110.1172/JCI151109