Effects of aging on liver microcirculatory function and sinusoidal phenotype.

Maeso-Díaz, Raquel; Ortega-Ribera, Martí; Fernández-Iglesias, Anabel; Hide, Diana; Muñoz, Leticia; Hessheimer, Amelia J; Vila, Sergi; Francés, Rubén; Fondevila, Constantino; Albillos, Agustín; Peralta, Carmen; Bosch, Jaime; Tacke, Frank; Cogger, Victoria C; Gracia Sancho, Jorge Sergio (2018). Effects of aging on liver microcirculatory function and sinusoidal phenotype. Aging cell, 17(6), e12829. Wiley 10.1111/acel.12829

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The socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
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

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Bosch, Jaime and Gracia Sancho, Jorge Sergio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1474-9726

Publisher:

Wiley

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

17 Dec 2018 11:08

Last Modified:

24 Oct 2019 03:07

Publisher DOI:

10.1111/acel.12829

PubMed ID:

30260562

BORIS DOI:

10.7892/boris.122125

URI:

https://boris.unibe.ch/id/eprint/122125

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