Student Queen's University Belfast Queen's University Belfast, Northern Ireland, United Kingdom
Abstract: Diabetes mellitus, a chronic disease characterised with low-grade inflammation, increases endothelial dysfunction and microbial infection risk. Bacteria that trigger epigenetic markers make endothelial cells, especially those from diabetics, susceptible. Histone Deacetylase 11 (HDAC11), an epigenetic regulator, is crucial to the inflammatory response and endothelial dysfunction. This work investigates how HDAC11 and STAT3 cause inflammation and endothelial dysfunction, shedding light on diabetes and associated vascular consequences. Using induced pluripotent stem cell-derived endothelial cells (iPS-ECs) from diabetic donors, this research demonstrates how HDAC11 expression is markedly upregulated upon stimulation with Escherichia coli (E. coli). The activation of HDAC11 was accompanied by a surge in pro-inflammatory cytokines and aggravated endothelial dysfunction, mimicking the chronic inflammatory state observed in diabetes. These findings highlight that HDAC11 plays a central role in amplifying the inflammatory cascade through its interaction with STAT3. Remarkably, when HDAC11 activity was inhibited, STAT3 activation was significantly reduced, leading to a decrease in cytokine production and a marked improvement in endothelial cell function. This study showed that HDAC11 is a key upstream regulator of STAT3, enhancing inflammatory signalling in response to bacterial infection. Targeting HDAC11 may allow early intervention in the inflammatory cascade and mitigate the diabetes-related vascular problems. The discovery of a direct epigenetic relationship between HDAC11 and STAT3 in diabetes is unique. This study shows that HDAC11 modulates inflammation and suggests that inhibiting this enzyme may treat endothelial dysfunction. Restoring endothelial function by inhibiting HDAC11 offers intriguing prospects for restoring vascular health and treating one of the most common and catastrophic diabetes consequences. In conclusion, our study sheds information about diabetes-related endothelial dysfunction and the involvement of HDAC11 in STAT3-mediated inflammation. New therapies targeting epigenetic regulators like HDAC11 may improve diabetic and cardiovascular outcomes by reducing vascular inflammation and dysfunction.
