NCOR1 and NCOR2 Exhibit Distinct Cellular and Transcriptomic Signatures in Human Abdominal Aortic Aneurysm

Area of Science:

• Vascular Biology
• Molecular Biology
• Epigenetics

Background:

• Nuclear receptor corepressors NCOR1 and NCOR2 regulate gene expression and chromatin.
• NCOR1 is linked to vascular biology, but NCOR2's role in abdominal aortic aneurysm (AAA) is unknown.
• Investigating NCOR1/2 in human AAA is crucial for understanding vascular disease.

Purpose of the Study:

• To examine the expression and cellular localization of NCOR1 and NCOR2 in human AAA.
• To identify molecular interactions of NCOR1 and NCOR2 within AAA tissue.
• To elucidate the potential roles of NCOR1/2 in AAA pathophysiology.

Main Methods:

• Analysis of human AAA and control aortic tissues (n=45 vs n=18).
• Transcriptomic profiling via RNA sequencing.
• Immunohistochemistry (IHC) for cellular localization.
• Differential expression and correlation analyses.

Main Results:

• No significant differences in bulk NCOR1 or NCOR2 transcript levels between AAA and controls.
• NCOR1 localized to endothelial cells, smooth muscle cells, and inflammatory cells.
• NCOR2 primarily localized to macrophages in AAA tissue.
• NCOR1 and NCOR2 showed distinct molecular associations with inflammatory mediators, epigenetic regulators, and signaling pathways.

Conclusions:

• Cell-type-specific roles for NCOR1 and NCOR2 in AAA are likely, despite absent bulk expression changes.
• NCOR1 and NCOR2 exhibit non-redundant functions in vascular remodelling, inflammation, and epigenetic regulation.
• NCOR pathways represent potential therapeutic targets for AAA.