d’Escamard, Valentina and Kadian-Dodov, Daniella and Ma, Lijiang and Lu, Sizhao and King, Annette and Xu, Yang and Peng, Shouneng and V′Gangula, Bhargravi and Zhou, Yu and Thomas, Allison and Michelis, Katherine C. and Bander, Emir and Bouchareb, Rihab and Georges, Adrien and Nomura-Kitabayashi, Aya and Wiener, Robert J. and Costa, Kevin D. and Chepurko, Elena and Chepurko, Vadim and Fava, Marika and Barwari, Temo and Anyanwu, Anelechi and Filsoufi, Farzan and Florman, Sander and Bouatia-Naji, Nabila and Schmidt, Lukas E. and Mayr, Manuel and Katz, Michael G. and Hao, Ke and Weiser-Evans, Mary C. M. and Björkegren, Johan L. M. and Olin, Jeffrey W. and Kovacic, Jason C. (2024) Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia. Nature Cardiovascular Research, 3 (9). pp.1098-1122. ISSN 2731-0590
Full text not available from this repository.Abstract
Fibromuscular dysplasia (FMD) is a poorly understood disease affecting 3-5% of adult females. The pathobiology of FMD involves arterial lesions of stenosis, dissection, tortuosity, dilation and aneurysm, which can lead to hypertension, stroke, myocardial infarction and even death. Currently, there are no animal models for FMD and few insights as to its pathobiology. In this study, by integrating DNA genotype and RNA sequence data from primary fibroblasts of 83 patients with FMD and 71 matched healthy controls, we inferred 18 gene regulatory co-expression networks, four of which were found to act together as an FMD-associated supernetwork in the arterial wall. After in vivo perturbation of this co-expression supernetwork by selective knockout of a top network key driver, mice developed arterial dilation, a hallmark of FMD. Molecular studies indicated that this supernetwork governs multiple aspects of vascular cell physiology and functionality, including collagen/matrix production. These studies illuminate the complex causal mechanisms of FMD and suggest a potential therapeutic avenue for this challenging disease.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 30 Dec 2024 05:05 |
| Last Modified: | 30 Dec 2024 05:05 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1602 |
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