Enhancing organ pool by statins: Is this the future?

Gracia‐Sancho, Jordi

doi:10.1111/j.1440-1746.2012.07160.x

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Considering the detrimental effects of WIR on liver microcirculation, KLF2 vasoprotective cascades, and recent data from our group demonstrating the beneficial effects of simvastatin in the cirrhotic liver 33 , we have applied an acute pharmacological pre-treatment with simvastatin to preserve liver endothelial function during WIR. Some previous experimental studies have applied statins to WIR and have shown benefits in terms of organ injury and inflammation 34 35 36 37 38 , however they have not evaluated the effects of statins on liver microvascular function and phenotype, especially when administered shortly before ischemia, thus discarding possible concomitant effects of lipid-lowering.…”

Section: Discussionmentioning

confidence: 99%

Effects of warm ischemia and reperfusion on the liver microcirculatory phenotype of rats: underlying mechanisms and pharmacological therapy

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Ortega‐Ribera

García-Pagán

et al. 2016

Sci Rep

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Warm ischemia and reperfusion (WIR) causes hepatic damage and may lead to liver failure, however the mechanisms involved are largely unknown. Here we have characterized the microcirculatory status and endothelial phenotype of livers undergoing WIR, and evaluated the use of simvastatin in WIR injury prevention. Male Wistar rats received simvastatin, or vehicle, 30 min before undergoing 60 min of partial warm ischemia (70%) followed by 2 h or 24 h of reperfusion. Hepatic and systemic hemodynamics, liver injury (AST, ALT, LDH), endothelial function (vasodilatation in response to acetylcholine), KLF2 and nitric oxide pathways, oxidative stress, inflammation (neutrophil and macrophage infiltration) and cell death were evaluated. Profound microcirculatory dysfunction occurred rapidly following WIR. This was evidenced by down-regulation of the KLF2 vasoprotective pathway, impaired vasodilatory capability and endothelial activation, altogether leading to increased hepatic vascular resistance and liver inflammation, with significant leukocyte infiltration, oxidative stress and cell death. Simvastatin preserved the hepatic endothelial phenotype, and blunted the detrimental effects of WIR on liver hemodynamics and organ integrity. In conclusion, WIR-induced injury to liver sinusoidal endothelial cells is mitigated by pre-treatment with Simvastatin probably through a KLF2-dependent mechanism.

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