J Biochem Mol Toxicol. 2026 Feb;40(2):e70719. doi: 10.1002/jbt.70719.
ABSTRACT
Endothelial dysfunction is a fundamental pathological process in atherosclerosis (AS), a leading cause of cardiovascular disease worldwide. The present study aimed to explore lncRNA ZEB2-AS1's expression, diagnostic value in AS, and its function on proliferation, inflammation, and potential mechanism in AS-related endothelial dysfunction. ZEB2-AS1 was detected in the specimens of 120 patients with AS and 115 control subjects, and the findings were validated using the GSE120521 dataset. An in vitro model of AS was established by inducing HUVECs with ox-LDL. In this model, ZEB2-AS1 expression was silenced. Assessment of cell viability was carried out with a CCK-8 kit. The secretion profiles of key inflammatory factors (TNF-α, IL-6, IL-1β), along with the chemokine MCP-1 and adhesion molecules (VCAM-1, ICAM-1), were analyzed by ELISA. Potential target miRNAs were predicted through LncRNASNP2 and miEAA databases, and miR-149-5p was verified using rescue experiments. Upregulation of ZEB2-AS1 was observed in the blood and tissues of individuals with AS, consistent with the data on unstable plaques from GSE120521. ZEB2-AS1 knockdown intensified the viability inhibition triggered by ox-LDL and decreased the secretion of inflammatory factors and adhesion molecules. miR-149-5p, a target molecule of ZEB2-AS1, exerted a reversing influence on these alterations. In conclusion, ZEB2-AS1 upregulation in AS promotes ox-LDL-induced endothelial dysfunction via miR-149-5p, acting as a potential AS biomarker/therapeutic target.
PMID:41642034 | DOI:10.1002/jbt.70719