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Plasma exosome-derived miRNA-887-5p alleviates high glucose- and lipid-induced endothelial cell dysfunction
Fangfang Xu1, Fang Chen2, Hui Xiao3
1Department of Phase I Clinical Trials Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Background:
Identifying differentially expressed miRNAs in plasma-derived exosomes associated with type 2 diabetes mellitus (T2DM) complicated by atherosclerosis (AS) and elucidating their roles in high-glucose/high-lipid-induced vascular endothelial dysfunction.
Methods:
Plasma-derived exosomal miRNAs were isolated from people with T2DM complicated by AS and healthy controls. Followed by miRNA sequencing to characterize differential expression profiles between groups. GO and KEGG pathway enrichment analyses were performed on differentially expressed miRNAs. Human umbilical vein endothelial cells (HUVECs) were exposed to combined hyperglycemia and hyperlipidemia to establish an in vitro model of diabetic endothelial injury. HUVECs were subsequently transfected with miR-887-5p mimics, inhibitors or negative controls, and assessed for proliferation, migration, apoptosis, oxidative stress, and nitric oxide (NO) content.
Results:
Sequencing revealed globally reduced plasma exosomal miRNA expression in people with T2DM and AS relative to healthy controls, with 21 upregulated and 23 downregulated miRNAs identified. Among these, hsa-miR-887-5p exhibited the greatest fold change of all detected miRNAs, while hsa-miR-96-5p and hsa-miR-183-5p (upregulated) and hsa-miR-410-3p (downregulated) harbored the most target genes implicated in diabetic atherosclerosis. Functionally, miR-887-5p enhanced HUVEC proliferation and migration under high-glucose/high-lipid conditions, elevated superoxide dismutase (SOD) activity, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, suppressed intracellular iNOS/NO and attenuated apoptosis.
Conclusion:
Plasma exosomal miRNA expression is broadly reduced in people with T2DM complicated by AS. hsa-miR-887-5p, hsa-miR-96-5p, hsa-miR-183-5p, and hsa-miR-410-3p may emerge as candidates with diagnostic and therapeutic relevance in this context. Specifically, miR-887-5p mitigates high-glucose/high-lipid-induced vascular endothelial injury, warranting further investigation as a therapeutic target.
