Abstract Body: Cancer survivors are at an increased risk for CVD mortality compared to the general population. Recent data suggest CTx-induced damage to the microvascular endothelium may contribute. Our preliminary studies suggest a roll for toll-like receptor 9 (TLR9) mediated inflammation in the onset of this pathology. TLR9 is activated by mitochondrial DNA (_mtDNA) fragments released from damaged tissue. Given CTx-induced tumor damage results in release of debris into the circulation, we tested the hypothesis that plasma samples obtained after CTx would contain higher levels of _mtDNA fragments than those obtained pre-CTx, and that this rise in plasma _mtDNA would correspond to impairments in microvascular endothelial function. To test this, we used qPCR to quantify _mtDNA fragments (D-Loop, ATPase 6-8) in plasma from hepatocellular carcinoma patients obtained prior to and 1-month post-CTx (ind. samples t-test, mean±SD). Videomicroscopy was used to assess microvascular function using healthy human adipose arterioles from surgical discard tissue. Arterioles were incubated for 15-20 hours with pre- or post-CTx plasma (10% dilution, intraluminal). Endothelium-dependent dilation (flow mediated dilation, FMD) was assessed at pressure gradients between 5 and 100 cmH2O (2-Way RM ANOVA, %max diameter±SD) whereas endothelium-independent dilation was assessed with 100µm papaverine (ind. samples t-test, %max diameter±SD). Plasma D-Loop was significantly elevated post-CTx compared to pre-CTx (post-CTx: n=12, 1.17±0.17 au; pre-CTx: n=8, 1.01±.15 au; p=0.04) whereas levels of ATPase 6-8 were not significantly different between conditions (post-CTx: n=12, 3.15±2.70 au; pre-CTx: n=8, 1.34±1.25 au; p=0.09). In arterioles treated with pre- and post-CTx plasma, a significant pressure gradient x group interaction was present (p=0.0003), with post-CTx (n=8) plasma samples impairing FMD to a greater degree than pre-CTx (n=5) samples. However, there were no differences between groups at individual pressure gradients (all P>0.05). Dilatory responses to papaverine were not different between groups (pre-CTx: n=5, 92±5%; post-CTx: n=8, 87±13%; p=0.43). In conclusion, these preliminary findings suggest a potential rise in plasma _mtDNA from pre-to post CTx which may contribute to the onset of CTx-induced microvascular endothelial dysfunction. Future work aims to determine the source of the _mtDNA (i.e., tumor vs healthy tissue) as well as the specificity of the _mtDNA-TLR9 axis in this pathology.