MiR-148a-3p/SIRT7 Axis Relieves Inflammatory-Induced Endothelial Dysfunction

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• MicroRNA-148a-3p (miR-148a-3p) plays a role in endothelial cell pathology, but its precise mechanism in inflammatory conditions remains unclear.
• Interleukin-6 (IL-6) is a key mediator of vascular dysfunction and inflammation.

Purpose of the Study:

• To investigate the role of miR-148a-3p in mitochondrial dysfunction and apoptosis in human aortic endothelial cells (teloHAECs) under IL-6 stimulation.
• To elucidate the molecular mechanism linking miR-148a-3p, SIRT7, and IL-6-induced endothelial inflammation.

Main Methods:

• Human aortic endothelial cells (teloHAECs) were treated with IL-6.
• miR-148a-3p expression, mitochondrial stress, and apoptosis were assessed.
• miR-148a-3p mimic was used to evaluate its protective effects.
• Bioinformatics analysis and dual-luciferase reporter assays were employed to validate the interaction between miR-148a-3p and SIRT7.

Main Results:

• IL-6 treatment decreased miR-148a-3p expression and increased SIRT7 levels, mitochondrial stress, and apoptosis in teloHAECs.
• Restoring miR-148a-3p levels using a mimic counteracted IL-6 effects, reducing cytokine release, apoptosis, and improving mitochondrial function.
• miR-148a-3p directly targets SIRT7 mRNA, downregulating its expression.

Conclusions:

• The miR-148a-3p/SIRT7 axis plays a critical role in mitigating mitochondrial damage and apoptosis in endothelial cells during inflammation.
• This pathway represents a novel therapeutic target for preventing IL-6-mediated endothelial dysfunction.