Sex differences and risk factors for bleeding in Alagille
syndrome

J 2022

Sex differences and risk factors for bleeding in Alagille syndrome

HANKEOVÁ, Simona, Van Hul NOEMI, Jakub LAZNOVSKY, Elisabeth VERBOVEN, Katrin MANGOLD et. al.

Basic information

Original name

Sex differences and risk factors for bleeding in Alagille syndrome

Authors

HANKEOVÁ, Simona (203 Czech Republic, belonging to the institution), Van Hul NOEMI, Jakub LAZNOVSKY, Elisabeth VERBOVEN, Katrin MANGOLD, Naomi HENSENS, Csaba ADORI, Elvira VERHOEF, Tomas ZIKMUND, Feven DAWIT, Michaela KAVKOVA, Jakub SALPLACHTA, Marika SJÖQVIST, Bengt R JOHANSSON, Mohamed G HASSAN, Linda FREDRIKSSON, Karsten BAUMGÄRTEL, Vítězslav BRYJA (203 Czech Republic, belonging to the institution), Urban LENDAHL, Andrew JHEON, Florian ALTEN, Kristina Teär FAHNEHJELM, Björn FISCHLER, Jozef KAISER and Emma R ANDERSSON (guarantor)

Edition

EMBO Molecular Medicine, Wiley, 2022, 1757-4676

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.100

RIV identification code

RIV/00216224:14310/22:00128186

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.15252/emmm.202215809

UT WoS

000879733100001

Keywords in English

Alagille syndrome; Bleeding; Jagged1; Notch; Vasculature

Abstract

V originále

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.

Links

EE2.3.20.0180, research and development project

Name: Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny

GX19-28347X, research and development project

Name: Molekulární a funkční analýza biologie kasein kinázy 1

Investor: Czech Science Foundation

Citovat

HANKEOVÁ, Simona, Van Hul NOEMI, Jakub LAZNOVSKY, Elisabeth VERBOVEN, Katrin MANGOLD, Naomi HENSENS, Csaba ADORI, Elvira VERHOEF, Tomas ZIKMUND, Feven DAWIT, Michaela KAVKOVA, Jakub SALPLACHTA, Marika SJÖQVIST, Bengt R JOHANSSON, Mohamed G HASSAN, Linda FREDRIKSSON, Karsten BAUMGÄRTEL, Vítězslav BRYJA, Urban LENDAHL, Andrew JHEON, Florian ALTEN, Kristina Teär FAHNEHJELM, Björn FISCHLER, Jozef KAISER and Emma R ANDERSSON. Sex differences and risk factors for bleeding in Alagille syndrome. EMBO Molecular Medicine. Wiley, 2022, vol. 14, No 12, p. 1-23. ISSN 1757-4676. Available from: https://dx.doi.org/10.15252/emmm.202215809.

@article{2248111,
   author = {Hankeová, Simona and Noemi, Van Hul and Laznovsky, Jakub and Verboven, Elisabeth and Mangold, Katrin and Hensens, Naomi and Adori, Csaba and Verhoef, Elvira and Zikmund, Tomas and Dawit, Feven and Kavkova, Michaela and Salplachta, Jakub and Sjöqvist, Marika and Johansson, Bengt R and Hassan, Mohamed G and Fredriksson, Linda and Baumgärtel, Karsten and Bryja, Vítězslav and Lendahl, Urban and Jheon, Andrew and Alten, Florian and Fahnehjelm, Kristina Teär and Fischler, Björn and Kaiser, Jozef and Andersson, Emma R},
   article_number = {12},
   doi = {http://dx.doi.org/10.15252/emmm.202215809},
   keywords = {Alagille syndrome; Bleeding; Jagged1; Notch; Vasculature},
   language = {eng},
   issn = {1757-4676},
   journal = {EMBO Molecular Medicine},
   title = {Sex differences and risk factors for bleeding in Alagille syndrome},
   url = {https://www.embopress.org/doi/full/10.15252/emmm.202215809},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2248111
AU  - Hankeová, Simona - Noemi, Van Hul - Laznovsky, Jakub - Verboven, Elisabeth - Mangold, Katrin - Hensens, Naomi - Adori, Csaba - Verhoef, Elvira - Zikmund, Tomas - Dawit, Feven - Kavkova, Michaela - Salplachta, Jakub - Sjöqvist, Marika - Johansson, Bengt R - Hassan, Mohamed G - Fredriksson, Linda - Baumgärtel, Karsten - Bryja, Vítězslav - Lendahl, Urban - Jheon, Andrew - Alten, Florian - Fahnehjelm, Kristina Teär - Fischler, Björn - Kaiser, Jozef - Andersson, Emma R
PY  - 2022
TI  - Sex differences and risk factors for bleeding in Alagille syndrome
JF  - EMBO Molecular Medicine
VL  - 14
IS  - 12
SP  - 1-23
EP  - 1-23
PB  - Wiley
SN  - 17574676
KW  - Alagille syndrome
KW  - Bleeding
KW  - Jagged1
KW  - Notch
KW  - Vasculature
UR  - https://www.embopress.org/doi/full/10.15252/emmm.202215809
N2  - 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.
ER  -

HANKEOVÁ, Simona, Van Hul NOEMI, Jakub LAZNOVSKY, Elisabeth VERBOVEN, Katrin MANGOLD, Naomi HENSENS, Csaba ADORI, Elvira VERHOEF, Tomas ZIKMUND, Feven DAWIT, Michaela KAVKOVA, Jakub SALPLACHTA, Marika SJÖQVIST, Bengt R JOHANSSON, Mohamed G HASSAN, Linda FREDRIKSSON, Karsten BAUMGÄRTEL, Vítězslav BRYJA, Urban LENDAHL, Andrew JHEON, Florian ALTEN, Kristina Teär FAHNEHJELM, Björn FISCHLER, Jozef KAISER and Emma R ANDERSSON. Sex differences and risk factors for bleeding in Alagille syndrome. \textit{EMBO Molecular Medicine}. Wiley, 2022, vol.~14, No~12, p.~1-23. ISSN~1757-4676. Available from: https://dx.doi.org/10.15252/emmm.202215809.

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