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

## TL;DR

This study shows how a specific long noncoding RNA, SNHG5, worsens sepsis-related heart damage by boosting inflammation in blood vessel cells.

## Contribution

The study identifies a new regulatory pathway involving SNHG5, miR-377-3p, and METAP2 in sepsis-induced endothelial injury.

## Key findings

- SNHG5 is significantly upregulated in septic coronary arteries and serum.
- SNHG5 promotes METAP2 expression by acting as a ceRNA for miR-377-3p.
- Reducing SNHG5 or METAP2 decreases IL-8 secretion and endothelial cell death.

## Abstract

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.

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.

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.

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.