Abstract Body: Ischemia with no obstructive coronary artery (INOCA) is a common cause of hospitalizations, resulting in poor outcomes and diminished quality of life. A key element in the pathophysiology of INOCA is endothelial dysfunction, which leads to myocardial ischemia despite the absence of significant coronary artery obstruction. Effective management of endothelial dysfunction is essential for alleviating symptoms and preventing cardiovascular events in INOCA patients. Recent studies have highlighted diabetes mellitus (DM) as a significant contributor to INOCA complications by exacerbating endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs), which are known to regulate gene expression, have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, there is a lack of research evaluating miRNA biomarkers specifically in INOCA patients. In our study, we examined a panel of circulating miRNAs associated with the regulation of endothelial function in INOCA patients with and without DM. Using RT-qPCR, we analyzed miRNA expression in a cohort of consecutive patients undergoing percutaneous coronary intervention (PCI) who were confirmed to have INOCA. We measured the expression levels of a previously validated panel of miRNAs in INOCA patients with DM compared to those without DM. Specifically, we observed an increased expression of several miRNAs previously associated with endothelial dysfunction and decreased expression of miRNAs known to protect endothelial function. Further analyses revealed that among these miRNAs, miR-363-5p was significantly downregulated (P<0.001) and miR-92a-3p was significantly upregulated (P<0.001) in INOCA patients with DM compared to those without DM, as illustrated in the volcano plot in Figure 1. Taken together, our findings demonstrated significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their potential role as biomarkers for endothelial dysfunction in INOCA.