<b>Abstract ID 90416</b> <b>Poster Board 265</b> <b>Introduction:</b> Fibrosis plays a critical role in the pathophysiology of vascular diseases. We previously identified certain metalloproteinases, regulators of fibrosis, to be associated with the rupture of cerebral aneurysms. However, there are no studies that extensively evaluate the role of cellular pathways linked to fibrosis in intracranial aneurysms (IAs). <b>Objectives:</b> To identify and characterize, through transcriptomic analysis, genes related to fibrosis in cerebral endothelial cells of patients with intracranial aneurysms. <b>Materials and Methods:</b> From a repository of transcriptomic studies in human tissues (ARCHS4), we extracted the subset of samples from endothelial cells originating from IAs, both ruptured and unruptured. Differentially expressed genes associated with fibrosis (DEGAFs) were identified. Additionally, we conducted an analysis of pathway enrichment and protein-protein interaction with the DEGAFs. <b>Results:</b> For IAs vs. cortical arteries, we discovered four DEGAFs. Two of them upregulated (NOX4 and SDC1) and two downregulated (CFTR and FGFR2). Regarding rupture vs. unruptured IAs, we discovered 39 DEGAFs. A total of 29 of these genes were found to be upregulated, while ten were downregulated. The top five overexpressed genes, measured by log2FC values, were IL-10, VEGFA, OSM, SERPINA1, and HMOX1. The top five underexpressed genes were COMP, FGF7, SOD3, BMP4, and SMAD6. The top five enriched biological Gene Ontology (GO) pathways for upregulated DEGAFs in rupture vs. unruptured IAs were: cytokine-mediated signaling pathway (GO:0019221), regulation of angiogenesis (GO:0045765), regulation of vasculature development (GO:1901342), leukocyte migration (GO:0050900), and wound healing (GO:0042060). Conversely, when considering negatively regulated genes, the top five enriched GO terms included ureteric bud development (GO:0001657), mesonephric epithelium development (GO:0072163), mesonephric tubule development (GO:0072164), mesonephros development (GO:0001823), and regulation of ossification (GO:0030278). We constructed a protein-protein interaction network using the DEGAFs found in ruptured vs. unruptured IAs. We used the information provided by this network to identify the top five hub genes applying the degree method. The hub genes of our network were FN1, VEGFA, IL-10, PF4, and CXCR4, demonstrating strong relationship between inflammation and fibrosis in our network. <b>Conclusion:</b> Our findings underscore the significance of fibrosis related genes and pathways in the genesis of IAs, particularly accentuating their involvement in instances of IA rupture. Moreover, our identification of pivotal gene hubs within the fibrotic process of IAs rupture, previously targeted in pharmacological approaches for fibrosis-related diseases, presents a compelling rationale for evaluating these targets in preventing IA ruptures. However, further exploration through longitudinal in-vivo studies is imperative to discern whether our observed associations signify causal relationships or are consequential to the rupture of IAs. The authors declare no conflicts of interest. <b>Acknowledgements:</b> This study was supported by a FAPA grant from the Universidad de los Andes, awarded to Ricardo A. Peña-Silva.