Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome

Emily E. Juzwiak; Caitlin J. Bowen; Rhiannon Edwards; Leda Restrepo; Serena Lee; Cassie A. Parks; Anthony Zeng; Maya M. Black; Oscar E. Reyes Gaido; Emily E. Bramel; Dustin T. Shigaki; Michael A. Beer; Chiara Bellini; Harry C. Dietz; Elena Gallo MacFarlane

doi:10.1172/jci.insight.198202

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Juzwiak, E. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Bowen, C. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Edwards, R. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Restrepo, L. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Lee, S. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Parks, C. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Zeng, A. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Black, M. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Reyes Gaido, O. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Bramel, E. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Shigaki, D. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Beer, M. in: PubMed | Google Scholar |

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Bellini, C. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Dietz, H. in: PubMed | Google Scholar

¹McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

²Department of Bioengineering, Northeastern University, Boston, United States of America

³Department of Dermatology, Brigham and Women’s Hospital, Boston, United States of America

⁴Predoctoral training in Human Genetics and Molecular Biology, Johns Hopkins University, Baltimore, United States of America

⁵Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States of America

Find articles by Gallo MacFarlane, E. in: PubMed | Google Scholar |

JCI Insight. https://doi.org/10.1172/jci.insight.198202.
Copyright © 2026, Juzwiak et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published April 28, 2026 - Version history

Aortic dissection or rupture is a leading cause of mortality in vascular Ehlers-Danlos syndrome (VEDS), a disorder caused by mutations in the COL3A1 gene. Col3a1^G938D/+ mice recapitulate features of VEDS, including high risk of aortic rupture. As in people with VEDS, aortic risk in this model accelerates at the onset of puberty, especially in males. We identify developmentally regulated gene programs associated with this vulnerability and that are targeted by treatments that mitigate aortic risk. Both genetic and pharmacological inhibition of the androgen receptor (AR) eliminated survival differences between sexes, while treatment with a dual AR and mineralocorticoid receptor (MR) antagonist provided near-complete and durable protection in both sexes. Pathways targeted by dual AR/MR inhibition, including those related to extracellular matrix (ECM) organization and cell-ECM interactions, largely overlapped with those also modulated by isolated MR antagonism. Selective targeting of MR signaling emerged as an effective therapeutic strategy in both sexes that avoids sexual side effects in males.

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Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome

Emily E. Juzwiak,¹ Caitlin J. Bowen,¹ Rhiannon Edwards,¹ Leda Restrepo,¹ Serena Lee,² Cassie A. Parks,¹ Anthony Zeng,¹ Maya M. Black,¹ Oscar E. Reyes Gaido,³ Emily E. Bramel,⁴ Dustin T. Shigaki,⁵ Michael A. Beer,⁵ Chiara Bellini,² Harry C. Dietz,¹ and Elena Gallo MacFarlane¹

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Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome

Emily E. Juzwiak,1 Caitlin J. Bowen,1 Rhiannon Edwards,1 Leda Restrepo,1 Serena Lee,2 Cassie A. Parks,1 Anthony Zeng,1 Maya M. Black,1 Oscar E. Reyes Gaido,3 Emily E. Bramel,4 Dustin T. Shigaki,5 Michael A. Beer,5 Chiara Bellini,2 Harry C. Dietz,1 and Elena Gallo MacFarlane1

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Emily E. Juzwiak,¹ Caitlin J. Bowen,¹ Rhiannon Edwards,¹ Leda Restrepo,¹ Serena Lee,² Cassie A. Parks,¹ Anthony Zeng,¹ Maya M. Black,¹ Oscar E. Reyes Gaido,³ Emily E. Bramel,⁴ Dustin T. Shigaki,⁵ Michael A. Beer,⁵ Chiara Bellini,² Harry C. Dietz,¹ and Elena Gallo MacFarlane¹