Detail publikačního výsledku

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.

Originální název

Sex differences and risk factors for bleeding in Alagille syndrome

Anglický název

Sex differences and risk factors for bleeding in Alagille syndrome

Druh

Článek WoS

Originální abstrakt

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.

Anglický abstrakt

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.

Klíčová slova

Alagille syndrome; Bleeding; Jagged1; Notch; Vasculature

Klíčová slova v angličtině

Alagille syndrome; Bleeding; Jagged1; Notch; Vasculature

Autoři

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.

Rok RIV

2023

Vydáno

07.12.2022

Nakladatel

WILEY

Místo

HOBOKEN

ISSN

1757-4684

Periodikum

EMBO Molecular Medicine

Svazek

14

Číslo

12

Stát

Spolková republika Německo

Strany počet

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="1757-4676",
  url="https://www.embopress.org/doi/full/10.15252/emmm.202215809"
}