Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Introduction: Ischemia/reperfusion injury (IRI) causes significant morbidity in liver transplantation and other surgical scenarios. A better understanding of the molecular mechanisms of IRI is required so that new strategies for prevention and treatment can be developed. Histone deacetylases (HDACs) regulate diverse cellular processes. We have previously shown protection from renal IRI with pan-HDAC inhibition as well as by targeting one specific HDAC isoform, HDAC2, via inducible gene deletion. We wished to investigate the effect of HDAC2 gene deletion on liver IRI.
Methods: Male wild type C57BL/6 (WT) or whole body HDAC2-deficient (HDAC2-/-) mice were subjected to 70% liver ischemia for 60 minutes under strict temperature control. Plasma concentrations of ALT and AST were assessed at 24 and 48 hours post-injury.
Results: HDAC2-/- mice developed significantly less hepatocellular injury after liver IRI than WT mice as measured by serum ALT (p=0.002, Figure 1a). A trend towards protection from liver IRI as measured by serum AST was also noted (p=0.110, Figure 1b). WT mice had 37.5% seven-day mortality (3/8) when subjected to liver IRI, whereas HDAC2-/- mice universally survived (0/7, p=0.08).
Conclusion: Murine HDAC2 gene deletion leads to mitigation of liver injury after hepatic IRI with significant improvement in ALT and trends toward improvement in AST and survival, likely impacted by small numbers. This finding confirms that the significant protection previously demonstrated with HDAC2 deletion in renal IRI is experienced in other tissues and implicates HDAC2 modulation as a general strategy for improved tissue ischemia tolerance. Pharmacologic HDAC2 inhibition may offer a novel therapeutic strategy to avoid organ injury with surgeries requiring liver ischemia.
CITATION INFORMATION: Murken D, Aufhauser Jr D, Wang Z, Ge G, Hancock W, Levine M. Histone Deacetylase-2 Gene Deletion in Mice Mitigates Liver Ischemia/Reperfusion Injury. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Murken D, Jr DAufhauser, Wang Z, Ge G, Hancock W, Levine M. Histone Deacetylase-2 Gene Deletion in Mice Mitigates Liver Ischemia/Reperfusion Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/histone-deacetylase-2-gene-deletion-in-mice-mitigates-liver-ischemiareperfusion-injury/. Accessed December 12, 2019.
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