Publication detail

Sex differences and risk factors for bleeding in Alagille syndrome

Hankeova, S. Van Hul, N. Laznovsky, J. Verboven, E. Mangold, K. Hensens, N. Adori, C. Verhoef, E. Zikmund, T. Dawit, F. Kavkova, M. Salplachta, J. Sjoqvist, M. Johansson, BR.Hassan, MG. Fredriksson, L. Baumgartel, K. Bryja, V. Lendahl, U. Jheon, A. Alten, F. Fahnehjelm, KT. Fischler, B. Kaiser, J. Andersson, ER.

Original Title

Sex differences and risk factors for bleeding in Alagille syndrome

Type

journal article in Web of Science

Language

English

Original Abstract

Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1(Ndr/Ndr) mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1(Ndr/Ndr) mice, using retina as a model. Jag1(Ndr/Ndr) mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1(Ndr/Ndr) mice represent a new model for vascular compromise in ALGS.

Keywords

Alagille syndrome; Bleeding; Jagged1; Notch; Vasculature

Authors

Hankeova, S.; Van Hul, N.; Laznovsky, J.; Verboven, E.; Mangold, K.; Hensens, N.; Adori, C.; Verhoef, E.; Zikmund, T.; Dawit, F.; Kavkova, M.; Salplachta, J.; Sjoqvist, M.; Johansson, BR.;Hassan, MG.; Fredriksson, L.; Baumgartel, K.; Bryja, V.; Lendahl, U.; Jheon, A.; Alten, F.; Fahnehjelm, KT.; Fischler, B.; Kaiser, J.; Andersson, ER.

Released

7. 12. 2022

Publisher

WILEY

Location

HOBOKEN

ISBN

1757-4684

Periodical

EMBO Molecular Medicine

Year of study

14

Number

12

State

United Kingdom of Great Britain and Northern Ireland

Pages count

23

URL

https://www.embopress.org/doi/full/10.15252/emmm.202215809

BibTex

@article{BUT182351,
  author="Hankeova, S. and Van Hul, N. and Laznovsky, J. and Verboven, E. and Mangold, K. and Hensens, N. and Adori, C. and Verhoef, E. and Zikmund, T. and Dawit, F. and Kavkova, M. and Salplachta, J. and Sjoqvist, M. and Johansson, BR. and Hassan, MG. and Fredriksson, L. and Baumgartel, K. and Bryja, V. and Lendahl, U. and Jheon, A. and Alten, F. and Fahnehjelm, KT. and Fischler, B. and Kaiser, J. and Andersson, ER.",
  title="Sex differences and risk factors for bleeding in Alagille syndrome",
  journal="EMBO Molecular Medicine",
  year="2022",
  volume="14",
  number="12",
  pages="23",
  doi="10.15252/emmm.202215809",
  issn="1757-4684",
  url="https://www.embopress.org/doi/full/10.15252/emmm.202215809"
}