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Stimulation of Vascular Endothelial Cells Using Neutrophil Extracellular Traps in the Presence of Low-Density Lipoprotein
Published on: August 12, 2025
MicroRNA-328 ameliorates oxidized low-density lipoprotein-induced endothelial cells injury through targeting HMGB1 in
Chun-Yang Wu1, Zhao-Feng Zhou1, Bin Wang1
1Department of Cardiology, Yancheng Hospital Affiliated to Southeast University School of Medicine, Yancheng, China.
Abstract:
Atherosclerosis has been recognized as a chronic inflammatory disease, which can harden the vessel wall and narrow the arteries. MicroRNAs exhibit crucial roles in various diseases including atherosclerosis. However, so far, the role of miR-328 in atherosclerosis remains barely explored. Therefore, our study concentrated on the potential role of miR-328 in vascular endothelial cell injury during atherosclerosis. In our current study, we observed that oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) apoptosis and inhibited cell viability dose-dependently and time-dependently. In addition, indicated dosage of ox-LDL obviously triggered HUVECs inflammation and oxidative stress process. Then, it was found that miR-328 in HUVECs was reduced by ox-LDL. HUVECs apoptosis was greatly repressed and cell survival was significantly upregulated by overexpression of miR-328. Furthermore, mimics of miR-328 rescued cell inflammation and oxidative stress process induced by ox-LDL. Oppositely, inhibitors of miR-328 strongly promoted ox-LDL-induced endothelial cells injury in HUVECs. By using bioinformatics analysis, high-mobility group box-1 (HMGB1) was predicted as a downstream target of miR-328. HMGB1 has been reported to be involved in atherosclerosis development. The correlation between miR-328 and HMGB1 was validated in our current study. Taken these together, it was implied that miR-328 ameliorated ox-LDL-induced endothelial cells injury through targeting HMGB1 in atherosclerosis.
Insights
MicroRNA-328 protects against atherosclerosis by reducing inflammation and oxidative stress in endothelial cells. It targets high-mobility group box-1 (HMGB1), mitigating damage caused by oxidized low-density lipoprotein (ox-LDL).
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Pathology
Background:
- Atherosclerosis is a chronic inflammatory disease impacting blood vessels.
- MicroRNAs (miRNAs) are key regulators in various diseases, including atherosclerosis.
- The specific role of miR-328 in atherosclerosis has been underexplored.
Purpose of the Study:
- To investigate the role of miR-328 in endothelial cell injury during atherosclerosis.
- To determine how oxidized low-density lipoprotein (ox-LDL) affects miR-328 expression and endothelial cell function.
- To identify downstream targets of miR-328 involved in atherosclerosis.
Main Methods:
- Oxidized low-density lipoprotein (ox-LDL) was used to induce injury in human umbilical vein endothelial cells (HUVECs).
- Cell viability, apoptosis, inflammation, and oxidative stress were assessed.
- miR-328 mimics and inhibitors were used to modulate miR-328 levels.
- Bioinformatics analysis and experimental validation were employed to identify miR-328 targets.
Main Results:
- ox-LDL induced HUVEC apoptosis, reduced cell viability, and promoted inflammation and oxidative stress.
- ox-LDL treatment decreased miR-328 expression in HUVECs.
- Overexpression of miR-328 repressed ox-LDL-induced apoptosis and inflammation, while enhancing cell survival.
- Inhibition of miR-328 exacerbated ox-LDL-induced endothelial cell injury.
- High-mobility group box-1 (HMGB1) was identified as a direct downstream target of miR-328.
Conclusions:
- miR-328 plays a protective role against ox-LDL-induced endothelial cell injury in atherosclerosis.
- miR-328 ameliorates endothelial cell damage by targeting HMGB1.
- These findings highlight miR-328 as a potential therapeutic target for atherosclerosis.
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