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Rat models for Portosinusoidal Vascular Disease

ABSTRACT: Background: Porto-Sinusoidal Vascular Disorder (PSVD) involves a group of rare vascular liver diseases of unknown etiology that leads 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 3 different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (combination of FOLFOX and a selenium-enriched diet, Selfox model) treatment and characterized them at hemodynamic, 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 non-specific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat animal models and human data showed both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding hemostasis, 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 development of new therapeutic targets for this rare condition.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE229380 | GEO | 2024/03/14

REPOSITORIES: GEO

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