Decoding coronary artery calcification: metabolic reprogramming features and a promising circulating biomarker PXDN

Area of Science:

• Molecular Biology
• Genomics
• Cardiovascular Disease Research

Background:

• Coronary artery calcification (CAC) is a significant predictor of cardiovascular disease.
• The underlying metabolism-related molecular alterations in CAC are not well understood.
• There is a need for reliable biomarkers for early CAC detection and risk stratification.

Purpose of the Study:

• To investigate metabolism-related transcriptional changes associated with CAC.
• To identify potential circulating biomarkers for early detection and risk stratification of CAC.

Main Methods:

• Analysis of two transcriptomic datasets (GSE58150 and GSE211752).
• Differential gene expression analysis, Gene Set Enrichment Analysis (GSEA), and Weighted Gene Co-expression Network Analysis (WGCNA).
• Screening of biomarker candidates using LASSO regression and validation in a CAC mouse model.

Main Results:

• Identified 138 upregulated and 104 downregulated genes in CAC, with significant alterations in amino acid and vitamin metabolism.
• WGCNA highlighted the ME2 module's strong correlation with CAC, and GSEA indicated immune pathway activation and metabolic pathway suppression.
• PXDN was identified as a top biomarker candidate with strong diagnostic performance (AUC 0.95 and 0.83) and elevated expression in CAC.

Conclusions:

• CAC is linked to transcriptional alterations in metabolism-related pathways.
• PXDN emerges as a potential circulating biomarker for CAC, supporting non-invasive risk assessment.
• Further mechanistic studies on PXDN in CAC are warranted.