Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease.

Maeso-Díaz, Raquel; Ortega-Ribera, Martí; Lafoz, Erica; Lozano, Juan José; Baiges, Anna; Francés, Rubén; Albillos, Agustín; Peralta, Carmen; García-Pagán, Juan Carlos; Bosch, Jaime; Cogger, Victoria C; Gracia-Sancho, Jordi (2019). Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease. Aging and disease, 10(4), pp. 684-698. Aging and Disease 10.14336/AD.2019.0127

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Advanced chronic liver disease (aCLD) represents a major public health concern. aCLD is more prevalent and severe in the elderly, carrying a higher risk of decompensation. We aimed at understanding how aging may impact on the pathophysiology of aCLD in aged rats and humans and secondly, at evaluating simvastatin as a therapeutic option in aged animals. aCLD was induced in young (1 month) and old (16 months) rats. A subgroup of aCLD-old animals received simvastatin (5 mg/kg) or vehicle (PBS) for 15 days. Hepatic and systemic hemodynamic, liver cells phenotype and hepatic fibrosis were evaluated. Additionally, the gene expression signature of cirrhosis was evaluated in a cohort of young and aged cirrhotic patients. Aged animals developed a more severe form of aCLD. Portal hypertension and liver fibrosis were exacerbated as a consequence of profound deregulations in the phenotype of the main hepatic cells: hepatocytes presented more extensive cell-death and poorer function, LSEC were further capillarized, HSC over-activated and macrophage infiltration was significantly increased. The gene expression signature of cirrhosis significantly differed comparing young and aged patients, indicating alterations in sinusoidal-protective pathways and confirming the pre-clinical observations. Simvastatin administration for 15-day to aged cirrhotic rats improved the hepatic sinusoidal milieu, leading to significant amelioration in portal hypertension. This study provides evidence that aCLD pathobiology is different in aged individuals. As the median age of patients with aCLD is increasing, we propose a real-life pre-clinical model to develop more reliable therapeutic strategies. Simvastatin effects in this model further demonstrate its translational potential.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Bosch, Jaime and Gracia Sancho, Jorge Sergio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2152-5250

Publisher:

Aging and Disease

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

16 Jan 2020 16:28

Last Modified:

16 Jan 2020 16:28

Publisher DOI:

10.14336/AD.2019.0127

PubMed ID:

31440376

Uncontrolled Keywords:

Cirrhosis elderly hepatic sinusoid liver microcirculation portal hypertension

BORIS DOI:

10.7892/boris.137288

URI:

https://boris.unibe.ch/id/eprint/137288

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