Curcumin attenuates vascular calcification via the exosomal miR-92b-3p/KLF4 axis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Nanomedicine

Background:

• Vascular calcification (VC) is a prevalent pathological change in vascular diseases with poorly understood mechanisms.
• Curcumin (CUR), a natural polyphenol, exhibits cardiovascular benefits including anti-inflammatory and antioxidant effects.
• Exosomes mediate intercellular communication through their miRNA cargo, suggesting a role in VC regulation.

Purpose of the Study:

• To investigate if CUR attenuates VC by modulating exosomal miRNA secretion.
• To elucidate the molecular pathway involved in CUR's effect on VC.

Main Methods:

• In vivo and in vitro models of vascular calcification were established.
• Exosomes were isolated from vascular smooth muscle cells (VSMCs) and characterized.
• Functional assays, RT-qPCR, bioinformatics, and dual luciferase assays were employed to assess miR-92b-3p, KLF4, and RUNX2 interactions.

Main Results:

• CUR treatment and CUR-derived exosomes attenuated VSMC calcification.
• miR-92b-3p expression was upregulated in VSMCs and exosomes following CUR intervention.
• miR-92b-3p directly targeted KLF4, influencing RUNX2 expression and thereby mitigating VC in vivo and in vitro.

Conclusions:

• CUR attenuates vascular calcification through the exosomal miR-92b-3p/KLF4 signaling pathway.
• Exosomal miR-92b-3p plays a protective role against VC by downregulating KLF4 and RUNX2.
• CUR represents a promising therapeutic agent for vascular calcification.