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Sex differences and risk factors for bleeding in Alagille syndrome
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9728057/ https://www.ncbi.nlm.nih.gov/pubmed/36345711 http://dx.doi.org/10.15252/emmm.202215809 |
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author | Hankeova, Simona Van Hul, Noemi 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, Vitezslav Lendahl, Urban Jheon, Andrew Alten, Florian Fahnehjelm, Kristina Teär Fischler, Björn Kaiser, Jozef Andersson, Emma R |
author_facet | Hankeova, Simona Van Hul, Noemi 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, Vitezslav Lendahl, Urban Jheon, Andrew Alten, Florian Fahnehjelm, Kristina Teär Fischler, Björn Kaiser, Jozef Andersson, Emma R |
author_sort | Hankeova, Simona |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9728057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97280572022-12-08 Sex differences and risk factors for bleeding in Alagille syndrome Hankeova, Simona Van Hul, Noemi 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, Vitezslav Lendahl, Urban Jheon, Andrew Alten, Florian Fahnehjelm, Kristina Teär Fischler, Björn Kaiser, Jozef Andersson, Emma R EMBO Mol Med Articles 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. John Wiley and Sons Inc. 2022-11-08 /pmc/articles/PMC9728057/ /pubmed/36345711 http://dx.doi.org/10.15252/emmm.202215809 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Hankeova, Simona Van Hul, Noemi 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, Vitezslav Lendahl, Urban Jheon, Andrew Alten, Florian Fahnehjelm, Kristina Teär Fischler, Björn Kaiser, Jozef Andersson, Emma R Sex differences and risk factors for bleeding in Alagille syndrome |
title | Sex differences and risk factors for bleeding in Alagille syndrome |
title_full | Sex differences and risk factors for bleeding in Alagille syndrome |
title_fullStr | Sex differences and risk factors for bleeding in Alagille syndrome |
title_full_unstemmed | Sex differences and risk factors for bleeding in Alagille syndrome |
title_short | Sex differences and risk factors for bleeding in Alagille syndrome |
title_sort | sex differences and risk factors for bleeding in alagille syndrome |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9728057/ https://www.ncbi.nlm.nih.gov/pubmed/36345711 http://dx.doi.org/10.15252/emmm.202215809 |
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