What question did this study set out to answer?

The aim is to identify miRNAs in plasma-derived exosomes that contribute to endothelial dysfunction due to diabetes and to explore therapeutic targets.

July 7, 2026Open Access

Plasma exosome-derived miRNA-887-5p alleviates high glucose- and lipid-induced endothelial cell dysfunction

FXFangfang XuUniversity of Science and Technology of China FCFang ChenAnhui Medical University HXHui XiaoAnhui Medical University

Key Points

The aim is to identify miRNAs in plasma-derived exosomes that contribute to endothelial dysfunction due to diabetes and to explore therapeutic targets.
Plasma-derived exosomal miRNAs isolated from individuals with type 2 diabetes and healthy controls.
miRNA sequencing and pathway enrichment analyses were performed on differentially expressed miRNAs.
Human umbilical vein endothelial cells were exposed to high glucose and lipids, followed by transfection with miR-887-5p mimics and inhibitors.
Twenty-one upregulated and twenty-three downregulated miRNAs were identified in T2DM patients compared to healthy controls.
miR-887-5p significantly improved HUVEC proliferation (increased) and migration, reduced LDH and MDA levels (decreased), and suppressed NO production.
miR-887-5p enhanced SOD activity and attenuated apoptosis under hyperglycemic/hyperlipidemic conditions.

Abstract

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.

Ask AI

Helpful

Bookmark

View Full Paper