Epigenetics Mechanisms in Multiorgan Dysfunction Syndrome.

Abstract

Epigenetic mechanisms including deoxyribonucleic acid (DNA) methylation, histone modifications (eg, histone acetylation), and microribonucleic acids (miRNAs) have gained much scientific interest in the last decade as regulators of genes expression and cellular function. Epigenetic control is involved in the modulation of inflammation and immunity, and its dysregulation can contribute to cell damage and organ dysfunction. There is growing evidence that epigenetic changes can contribute to the development of multiorgan dysfunction syndrome (MODS), a leading cause of mortality in the intensive care unit (ICU). DNA hypermethylation, histone deacetylation, and miRNA dysregulation can influence cytokine and immune cell expression and promote endothelial dysfunction, apoptosis, and end-organ injury, contributing to the development of MODS after a critical injury. Epigenetics processes, particularly miRNAs, are emerging as potential biomarkers of severity of disease, organ damage, and prognostic factors in critical illness. Targeting epigenetics modifications can represent a novel therapeutic approach in critical care. Inhibitors of histone deacetylases (HDCAIs) with anti-inflammatory and antiapoptotic activities represent the first class of drugs that reverse epigenetics modifications with human application. Further studies are required to acquire a complete knowledge of epigenetics processes, full understanding of their individual variability, to expand their use as accurate and reliable biomarkers and as safe target to prevent or attenuate MODS in critical disease.