Decreased expression of RPL15 and RPL18 exacerbated the calcification of valve interstitial cells during aortic valve...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Genomics

Background:

• Calcific aortic valve disease (CAVD) is the most prevalent valvular heart condition, with rising incidence due to global aging.
• The complex pathobiology of CAVD remains incompletely understood, necessitating further research into its underlying mechanisms.

Purpose of the Study:

• To identify differentially expressed genes (DEGs) in calcified aortic valve tissues.
• To analyze the correlation between these DEGs and clinical features in CAVD patients.
• To uncover potential therapeutic targets for CAVD.

Main Methods:

• Microarray analysis to screen for DEGs in normal versus CAVD tissues.
• Quantitative real-time PCR to validate DEG expression.
• Bioinformatic analyses, including protein-protein interaction network construction.
• Correlation analysis between gene expression and clinical markers of osteogenic differentiation.

Main Results:

• 1048 DEGs identified in calcified aortic valve tissues (227 upregulated, 821 downregulated).
• Top 5 hub genes identified: RPL15, RPL18, RPL18A (60S ribosomal subunit), RPS15, RPS21 (40S ribosomal subunit).
• Significantly decreased expression of RPL15 and RPL18 observed in calcified tissues, negatively correlated with OPN (osteogenic marker).
• Inhibition of RPL15 or RPL18 worsened valve interstitial cell calcification.

Conclusions:

• Reduced expression of RPL15 and RPL18 is strongly associated with aortic valve calcification.
• These ribosomal genes represent promising therapeutic targets for managing CAVD.
• Further investigation into the role of RPL15 and RPL18 in CAVD pathogenesis is warranted.