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2024-01

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cc by-nc-nd (c) Campreciós Figueras, Genís et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/220686

Interspecies transcriptomic comparison identifies a potential porto-sinusoidal vascular disorder rat model suitable for in vivo drug testing.

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https://doi.org/10.1111/liv.15765

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Background: Porto-sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life-threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease. Methods: We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium-enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data. Results: All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD-specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model. Conclusions: The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition.

Matèries

Malalties del fetge, Malalties vasculars, Models animals en la investigació

Matèries (anglès)

Liver diseases, Vascular diseases, Animal models in research

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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CAMPRECIÓS FIGUERAS, Genís, VILASECA BARCELÓ, Marina, TRIPATHI, Dinesh, MONTIRONI, Carla, DÍAZ, Alba, AGUILAR, Daniel, GARCÍA CALDERÓ, Héctor, MONTAÑÉS, Rosa, ANTON, Aina, HERNÁNDEZ GEA, Virginia, GARCÍA PAGÁN, Juan carlos. Interspecies transcriptomic comparison identifies a potential porto-sinusoidal vascular disorder rat model suitable for in vivo drug testing.. _Liver International_. 2024. Vol. 44, núm. 1, pàgs. 180-190. [consulta: 24 de gener de 2026]. ISSN: 1478-3223. [Disponible a: https://hdl.handle.net/2445/220686]

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