Endothelial Cells retain inflammatory memory through chromatin remodeling

Sepsis survivors exhibit long-term endothelial dysfunction, increasing susceptibility to secondary infections such as pneumonia. To investigate the epigenetic and transcriptional basis of endothelial inflammatory memory, we employed transcriptomic profiling of primary endothelial cells exposed to inflammatory stimuli in a two-hit model. This study reveals persistent transcriptional reprogramming following IL-6 exposure and identifies a primed endothelial state that amplifies responses to secondary challenges. Overall design: Primary endothelial cells were treated with IL-6 or PBS for 72 hours (first hit), followed by a 48-hour washout phase. Cells were then challenged with either LPS or PBS for 6 hours (second hit). Total RNA was extracted from 18 samples across six experimental conditions: IL6_72h, IL6_72h_W48h, IL672h_W48h_LPS, PBS_72h, PBS_72h_W48h, and PBS72h_W48h_LPS, each with three biological replicates. RNA-seq was performed using the Illumina NovaSeq 6000 platform (paired-end). The resulting data were analyzed to identify genes associated with inflammatory memory.