GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306399/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306399GEOGSEfalseTranscriptomic changes in HUVEC with PDL1 knockdownProgrammed cell death ligand-1 (PD-L1) is an immune checkpoint protein expressed in vascular endothelial cells (ECs). In contrast to cancer, our understanding of endothelial PD-L1 in relation to metabolic syndromes and its vascular complications is less studied. For example, its regulation and intrinsic function remain unclear. Here, we show endothelial PD-L1 is regulated by leptin receptor signaling. In particular, endothelial PD-L1 expression is likely affected by leptin resistance. A lack of leptin receptors leads to PD-L1 downregulation in vascular ECs via post-translational degradation. To understand the fundamental roles of endothelial PD-L1, RNA interference and selective knockout are employed in human endothelium and animals, respectively. Silencing or deleting endothelial PD-L1 expression delays the cycle progression and proliferation, because of Ras/MAPK inactivation. During obesity, endothelial PD-L1 deficiency impairs the EC turnover and worsened the vascular function. Overall, we provide a new insight of how endothelial PD-L1 contributes to vascular homeostasis, suggesting its pathophysiological importance in maintaining cellular turnover.2026/10/02GSE306399GSM9198838GSM9198837GSM9198836GSM9198835GSM9198834GSM919883324676306399Homo sapiens