Dynamic Gene Expression Signatures across Stages of Carotid Plaque Calcification

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Translational Research

Background:

• Carotid artery plaque calcification is a hallmark of atherosclerosis.
• The biological processes driving plaque maturation and calcification are not fully understood.

Purpose of the Study:

• To investigate gene expression profiles across different stages of carotid artery plaque calcification.
• To elucidate the dynamic biological processes involved in plaque maturation.

Main Methods:

• Carotid plaque specimens were categorized into four calcification severity groups using CT calcium scoring.
• RNA sequencing (SMART-Seq) and qRT-PCR were employed to analyze gene expression related to VSMC phenotype, inflammation, ECM, and calcification.

Main Results:

• Mildly calcified plaques showed increased inflammatory and osteogenic gene expression.
• Moderately calcified plaques exhibited transient suppression of these genes with ELN upregulation.
• Severely and very severely calcified plaques displayed persistent osteogenic/inflammatory markers, VSMC gene downregulation, and ECM remodeling, indicating stabilization.

Conclusions:

• Carotid plaque calcification is a dynamic, multistage process involving VSMC phenotype and ECM remodeling.
• Calcification is an active remodeling process, not just passive deposition.
• Findings may inform the development of stage-specific therapeutic strategies for carotid artery disease.