Curcumin inhibits calcification of human aortic valve interstitial cells by interfering NF-κB, AKT, and ERK pathways

Area of Science:

• Cardiovascular Biology
• Cellular Mechanisms of Disease
• Molecular Pharmacology

Background:

• Osteogenic differentiation of human aortic valve interstitial cells (hVICs) drives calcified aortic valve disease (CAVD).
• Understanding the molecular pathways involved is crucial for developing effective treatments.

Purpose of the Study:

• To investigate how curcumin (CCM) inhibits hVIC osteogenic differentiation.
• To elucidate the underlying molecular mechanisms of CCM's action.

Main Methods:

• hVICs were cultured under osteogenic medium (OM) conditions with and without CCM.
• Osteogenesis markers (calcified nodule formation, ALP, Runx2) were assessed.
• RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed.
• Western blotting was used to evaluate signaling pathway activation (ERK, IκBα, AKT, P65).

Main Results:

• CCM significantly inhibited OM-induced calcified nodule formation and osteogenesis markers in hVICs.
• RNA sequencing identified key differentially expressed genes.
• KEGG analysis highlighted enrichment in NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways.
• CCM suppressed phosphorylation of ERK, IκBα, and AKT, and inhibited P65 nuclear translocation.

Conclusions:

• CCM effectively inhibits hVIC osteogenic differentiation.
• CCM exerts its inhibitory effects by interfering with the activation of NF-κB/AKT/ERK signaling pathways.
• These findings highlight CCM's potential as a therapeutic agent for CAVD.