Finally, a gene set enrichment analysis of hearts of patients with septic, ischemic or dilated cardiomyopathy revealed a sepsis-specific suppression of SIRT3 deacetylation targets, including ATP5A1, indicating a functional relevance of SIRT3-dependent pathways in human sepsis.
Here, we show that nuclear SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogenesis, which alters bioenergetics during sepsis adaptation.
Our results suggest that polydatin protects against LPS-induced endothelial barrier disruption dependent on SIRT3 and can be applied as a potential therapy for sepsis.