2026-10-11T13:18:48Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32826122 2026-10-01T16:10:34Z portal_1172 item_type_8 month_year_10_2026

Modelling human vascular diabetes and deciphering epigenetic regulation in diabetes-associated infections Wiwit Ananda Wahyu Setyaningsih (23556983) PUREID: 659414159 diabetes infections vascular inflammation STAT3 HDAC11 iPS-ECs epigenetic memory Diabetes mellitus (DM) is a chronic metabolic disease that leads to various vascular complications. Individuals with diabetes are at a higher risk of developing infections, including bacterial infections, due to impaired immune responses. Escherichia coli (E. coli), a Gram-negative bacterium, is commonly associated with diabetes-related infections such as urinary tract infections (UTIs), diabetic foot ulcers, and sepsis. Endothelial cells (ECs) form the inner lining of blood vessels and the lymphatic system, directly interacting with blood and circulating immune cells. This thesis elucidated the involvement of epigenetic regulators in aggravating inflammation in ECs derived from diabetic (DB) donors in response to E. coli infection. ECs derived from induced pluripotent stem cells (iPS-ECs) were used in this study as a model to investigate E. coli-induced infection. The study demonstrated that E. coli infection induced an inflammatory response in iPS-ECs derived from both non-diabetic (ND) and diabetic (DB) donors, as evidenced by elevated levels of pro-inflammatory cytokines, chemokines, and adhesion molecules. These effects were more pronounced in DB donors and were accompanied by increased reactive oxygen species (ROS) production and endothelial dysfunction. To further investigate why diabetic iPS-ECs exhibited a stronger inflammatory response, we found that HDAC11expression was significantly upregulated in DB iPS-ECs and became even more evident in the presence of E. coli. In conclusion, this study demonstrated that E. coli infection induced inflammation and endothelial dysfunction in iPS-ECs derived from DB donors and highlighted HDAC11 as a potential mechanistic link between diabetes and the exacerbation of inflammatory responses during E. coli infection. Thesis is embargoed until 31 December 2026. 2026-10-01T16:10:34Z Text Thesis 10.17034/32826122.v1 https://figshare.com/articles/thesis/Modelling_human_vascular_diabetes_and_deciphering_epigenetic_regulation_in_diabetes-associated_infections/32826122 All Rights Reserved Open Access after 2026-12-31