Genome wide DNA methylation and transcriptome integration analysis reveals potential markers in type A aortic...

Area of Science:

• Vascular Biology
• Epigenetics
• Genomics

Background:

• Type A aortic dissection (TAAD) is a life-threatening vascular condition with high mortality.
• The epigenetic mechanisms, particularly gene methylation, underlying TAAD pathogenesis remain underexplored.

Purpose of the Study:

• To identify novel candidate diagnostic markers for TAAD by integrating gene methylation and transcriptome data.
• To investigate the functional role of identified methylated genes in vascular smooth muscle cells.

Main Methods:

• Integration of methylation and transcriptome sequencing data from TAAD and control aortic tissues.
• Bioinformatics analyses, including differential analysis, protein-protein interaction networks, and machine learning algorithms.
• In vitro experiments using human vascular smooth muscle cells (HVSMCs) to assess gene function.

Main Results:

• Identified 239 differentially methylated genes, primarily involved in nicotinamide nucleotide metabolism.
• Discovered three key methylated genes (ZC3H12A, IRAK2, CCL5) as potential TAAD markers.
• ZC3H12A was found to promote HVSMC proliferation and migration while inhibiting phenotypic switching, with its expression negatively correlated with methylation levels.

Conclusions:

• ZC3H12A, IRAK2, and CCL5 are potential diagnostic biomarkers for Type A aortic dissection.
• ZC3H12A may play a significant role in TAAD progression by influencing vascular smooth muscle cell behavior.