Spatial transcriptomic analysis reveals spatial features in human Stanford type A aortic dissection

Area of Science:

• Cardiovascular Biology
• Molecular Pathology
• Genomics

Background:

• Stanford type A aortic dissection (AAD) is a critical cardiovascular condition.
• AAD involves a tear in the aortic wall, posing a significant health risk.

Purpose of the Study:

• To comprehensively analyze molecular changes in ascending aortas from AAD patients.
• To identify molecular signatures associated with AAD severity and progression.
• To explore potential biomarkers and therapeutic targets for AAD.

Main Methods:

• Spatial transcriptomics and multiplex immunofluorescence were employed.
• Ascending aortas from eight AAD patients of varying severities and segments were analyzed.
• Gene expression patterns and protein markers were investigated.

Main Results:

• SPP1-driven inflammatory signaling was found to intensify with increasing AAD severity.
• A nine-gene severity scale (MYL6/CALD1/MYH9 for mild, CCL2/CP/COL4A1 for moderate, TMSB4X/ATP5F1E/PKM for severe) was identified.
• A collagen-remodeling gene triad (COL1A1/COL3A1/MMP2) was upregulated in specific arteries, potentially preceding ascending aortic changes.

Conclusions:

• Molecular signatures, including the SPP1-inflammatory axis and collagen remodeling, offer insights into AAD mechanisms.
• These findings support the development of non-invasive biomarkers for risk stratification.
• The identified molecular pathways present targets for precision pharmacotherapy in AAD treatment.