SNHG5 Exacerbates Sepsis-Induced Inflammatory Injury in Coronary Artery Endothelial Cells by Regulating METAP2-Mediated IL-8 Secretion.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in regulating inflammatory responses in sepsis. This study aimed to investigate the potential roles of lncRNA SNHG5 in the pathogenesis of sepsis-induced coronary artery injury. METHODS: Cecal ligation and puncture were used to establish a sepsis mouse model. Serum and coronary artery tissues were collected to assess inflammatory markers and lncRNA expression using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qPCR). In vitro, mouse aortic endothelial cells were exposed to septic serum. The SNHG5/miR-377-3p/methionyl aminopeptidase 2 (METAP2) axis was investigated using dual-luciferase reporter gene experiments. Loss-of-function, gain-of-function, and rescue assays were performed to elucidate the functions of these genes in sepsis. RESULTS: Septic mice exhibited elevated systemic tumor necrosis factor alpha and interleukin (IL)-6 levels, as well as dysregulated endothelial markers (eNOS downregulation and ET-1 upregulation). Among the inflammation-related lncRNAs, SNHG5 was the most significantly upregulated in septic coronary arteries and serum. Bioinformatic and experimental analyses revealed that SNHG5 acts as a competitive endogenous RNA (ceRNA) for miR-377-3p, thereby upregulating (METAP2). Silencing SNHG5 or METAP2 reduced IL-8 secretion and endothelial apoptosis; these effects were reversed by miR-377-3p inhibition. Conversely, METAP2 overexpression increased IL-8 secretion and apoptosis, which were attenuated by miR-377-3p mimics. CONCLUSION: We identified the SNHG5/miR-377-3p/METAP2 axis as a novel regulatory pathway in sepsis-induced endothelial inflammation and apoptosis. SNHG5 promotes METAP2 expression by sponging miR-377-3p, leading to increased IL-8 secretion and endothelial dysfunction. These findings provide new insights into lncRNA-mediated mechanisms in sepsis.