Arteriovenous fistulas (AVFs), created for
hemodialysis in
end-stage renal disease patients, mature through the outward remodeling of the outflow vein. However, early
thrombosis and chronic
inflammation are detrimental to the process of AVF maturation and precipitate AVF maturation failure. For the successful remodeling of the outflow vein, blood flow through the
fistula is essential, but early arterial
thrombosis attenuates this blood flow, and the vessels become thrombosed and stenosed, leading to AVF failure. The altered expression of various
proteins involved in maintaining vessel patency or
thrombosis is regulated by genes of which the expression is regulated by
transcription factors and
microRNAs. In this study, using thrombosed and stenosed arteries following AVF creation, we delineated
transcription factors and
microRNAs associated with differentially expressed genes in bulk
RNA sequencing data using upstream and causal network analysis. We observed changes in many
transcription factors and
microRNAs that are involved in angiogenesis; vascular smooth muscle cell proliferation, migration, and phenotypic changes; endothelial cell function;
hypoxia; oxidative stress; vessel remodeling; immune responses; and
inflammation. These factors and
microRNAs play a critical role in the underlying molecular mechanisms in AVF maturation. We also observed epigenetic factors involved in gene regulation associated with these molecular mechanisms. The results of this study indicate the importance of investigating the transcriptional and epigenetic regulation of AVF maturation and maturation failure and targeting factors precipitating early
thrombosis and
stenosis.