Your browser doesn't support javascript.
loading
Interspecies transcriptomic comparison identifies a potential porto-sinusoidal vascular disorder rat model suitable for in vivo drug testing.
Campreciós, Genís; Vilaseca, Marina; Tripathi, Dinesh M; Montironi, Carla; Díaz, Alba; Aguilar, Daniel; García-Calderó, Héctor; Montañés, Rosa; Anton, Aina; Hernández-Gea, Virginia; García-Pagán, Joan Carles.
Afiliação
  • Campreciós G; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain.
  • Vilaseca M; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
  • Tripathi DM; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
  • Montironi C; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain.
  • Díaz A; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
  • Aguilar D; Liver Physiology & Vascular Biology Group, Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences (ILBS), Vasant Kunj, New Delhi, India.
  • García-Calderó H; Pathology Department & Molecular Biology Core, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Catalonia, Spain.
  • Montañés R; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
  • Anton A; Pathology Department, Biomedical Diagnostic Centre, Hospital Clínic Barcelona, Barcelona, Catalonia, Spain.
  • Hernández-Gea V; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
  • García-Pagán JC; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Catalonia, Spain.
Liver Int ; 44(1): 180-190, 2024 01.
Article em En | MEDLINE | ID: mdl-37872644
ABSTRACT

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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Hipertensão Portal Limite: Animals / Humans Idioma: En Revista: Liver Int Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Hipertensão Portal Limite: Animals / Humans Idioma: En Revista: Liver Int Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha