{
  "abstract": "Introduction The formation, growth, and rupture of intracranial aneurysms (IAs) is a multi-faceted process that involves constant IA wall damage and repair. Intra-aneurysmal hemodynamics and endothelial dysfunction are key contributors towards this. However, the mechanistic link connecting the two is grossly understudied.Objective The aim of this study is to identify differences in transcriptomics and pathways of endothelial cells (EC) between control, unruptured (UIAs) and ruptured intracranial aneurysms (RIAs). A secondary aim was to better understand correlation between intra-aneurysmal hemodynamics and gene expression levels IAs.Methods ECs were obtained from peripheral access arteries and IAs using minimally invasive endoluminal biopsy during endovascular treatment of IAs. We then performed differential gene expression, pathway enrichment and network analysis between control and IA ECs and between UIAs and RIAs to identify key genes and pathways involved in IA formation and rupture. For IA cases, we also performed patient specific CFD analysis to identify potential correlation between local hemodynamics and gene expression levels.Results We analyzed a total of 158 ECs from control locations and 95 from IAs across 14 patients. Seven genes (S100A8, S100A9, FTL, FTH1, SH3BGRL3, COX4I1 and BTN3A2) were significantly overexpressed in IA cases (p<0.05). S100A8 and S100A9 are genes associated with inflammation, immune response and phagocytosis. Similarly, FTL and FTH1 are involved in lipid peroxidation which leads to ferroptosis of cells and endothelial dysfunction. Pathway analysis demonstrated cellular response to stress, necroptosis, dysregulated iron uptake and inflammation related pathways to be enriched in IAs compared with control cells. Comparing UIAs with RIAs we found ETS1, MAVS, FYN, WIPF1, SMAD2 and CDC42SE2 to be overexpressed in RIAs. FYN and WIPF1 are involved in the cellular response to stress pathway had a higher expression in RIAs. FYN is responsible for higher inflammation and reduction in autophagy. Similarly, ETS1, SMAD2 and CDC42 are responsible for local inflammation. Higher values could suggest inflammation driven by local hemodynamic insult. Indeed, through univariate analysis we found that wall shear stress was significantly lower in cases with higher gene expression suggesting infiltration of inflammatory cells causing wall weakening and rupture.Conclusion We observed that endothelial dysfunction plays a major role in IA formation through dysregulated iron uptake, inflammation and cellular stress. Hemodynamic stress in IAs can alter EC transcriptomics potentially leading to IA progression and rupture.Disclosures S. Veeturi: None. S. Dabb: None. K. Budohoski: None.Abstract E-122 Figure 1A) Dot plot of enriched pathways between control and IA ECs. Cellular response to stress is the pathway with the highest score. B) Differences in normalized wall shear stress between high and low gene expression cases",
  "authors": [
    {
      "affiliations": [
        "Neurosurgery, University of Utah, Salt Lake City, UT"
      ],
      "name": "S Veeturi"
    },
    {
      "affiliations": [
        "Neurosurgery, University of Utah, Salt Lake City, UT"
      ],
      "name": "AS Liang"
    },
    {
      "affiliations": [
        "Neurosurgery, University of Utah, Salt Lake City, UT"
      ],
      "name": "S Dabb"
    },
    {
      "affiliations": [
        "Neurosurgery, University of Utah, Salt Lake City, UT"
      ],
      "name": "K Budohoski"
    }
  ],
  "title": "E-122 Single cell transcriptomics of endothelial cells reveals novel pathways for aneurysm formation and rupture",
  "uid": "e08fd17a-c2c5-54b0-8126-b130b98bdc3f"
}