Endothelial cells displayed the second most DEGs in OUD. Upregulated pathways in endothelial cells included several growth factors, VEGFR, EGFR, and PDGFR88,89 (Fig. 5c). Several of these growth factors are linked to nociception and opioid tolerance89,90. Other pathways included leukocyte chemotaxis and dendrite morphogenesis. Among the densely connected endothelial pathways, the top significantly upregulated hub gene was the brain-specific angiogenesis inhibitor 1-associated protein 2, BAIAP2 (log2FC = 2.31, FDR = 0.0017), and, interestingly, the Alzheimer’s related microtubule-associated protein tau, MAPT (log2FC = 1.58, FDR = 0.036). The upregulation of MAPT may contribute to neurovascular brain insults in OUD6,91.
