Creating a "Prosurvival phenotype" through histone deacetylase inhibition: Past, present, and future

Ihab Halaweish, Vahagn Nikolian, Patrick Georgoff, Yongqing Li, Hasan B. Alam*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

Traumatic injuries and their sequelae represent a major source of mortality in the United States and globally. Initial treatment for shock, traumatic brain injury, and polytrauma is limited to resuscitation fluids to replace lost volume. To date there are no treatments with inherent prosurvival properties. Our laboratory has investigated the use of histone deacetylase inhibitors (HDACIs) as pharmacological agents to improve survival. This class of drugs acts through posttranslational protein modifications and is a direct regulator of chromatin structure and function, as well as the function of numerous cytoplasmic proteins. In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a significant survival advantage, even in the absence of fluid resuscitation. Positive results have also been shown in two-hit models of hemorrhage and sepsis and in hemorrhagic shock combined with traumatic brain injury. Accumulating data generated by our group and others continue to support the use of HDACIs for the creation of a prosurvival phenotype. With further research and clinical trials, HDACIs have the potential to be an integral tool in the treatment of trauma, especially in the prehospital phase.

Original languageEnglish (US)
Pages (from-to)6-16
Number of pages11
JournalShock
Volume44
DOIs
StatePublished - Aug 2015
Externally publishedYes

Keywords

  • Epigenetic
  • Genes
  • Hemorrhage
  • Histone deacetylase inhibitor
  • Inflammation
  • Proteins
  • Sepsis
  • Shock
  • Survival
  • Traumatic brain injury

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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