Ischemia/reperfusion injury in the aged liver: The importance of the sinusoidal endothelium in developing therapeutic strategies for the elderly.

Hide, Diana; Warren, Alessandra; Fernández-Iglesias, Anabel; Maeso-Díaz, Raquel; Peralta, Carmen; Le Couteur, David G; Bosch, Jaime; Cogger, Victoria C; Gracia-Sancho, Jordi (2020). Ischemia/reperfusion injury in the aged liver: The importance of the sinusoidal endothelium in developing therapeutic strategies for the elderly. The journals of gerontology. Series A, Biological sciences and medical sciences, 75(2), pp. 268-277. Oxford University Press 10.1093/gerona/glz012

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The liver endothelium plays a key role in the progression and resolution of liver diseases in young and adult individuals. However, its role in older people remains unknown. We have herein evaluated the importance of the sinusoidal endothelium in the pathophysiology of acute liver injury, and investigated the applicability of simvastatin, in aged animals.18 months old male Wistar rats underwent 60 min of partial warm ischemia followed by 2h of reperfusion (WIR). A group of aged rats received simvastatin for 3 days before WIR. Endothelial phenotype, parenchymal injury, oxidative and nitrosative stress, and fenestrae dynamics were analysed. The effects of WIR and simvastatin were investigated in primary LSEC from aged animals.The results of this study demonstrated that WIR significantly damages the liver endothelium and its effects are markedly worse in old animals. WIR-aged livers exhibited reduced vasodilation and sinusoidal capillarization, associated with liver damage and cellular stress. Simvastatin prevented the detrimental effects of WIR in aged livers.In conclusion, the liver sinusoidal endothelium of old animals is highly vulnerable to acute insult, thus targeted protection is especially relevant in preventing liver damage. Simvastatin represents a useful therapeutic strategy in aging.

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)
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:

1758-535X

Publisher:

Oxford University Press

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

16 Jan 2020 15:58

Last Modified:

22 Jan 2020 01:33

Publisher DOI:

10.1093/gerona/glz012

PubMed ID:

30649272

BORIS DOI:

10.7892/boris.137296

URI:

https://boris.unibe.ch/id/eprint/137296

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