Molecular role of Cx37 in advanced atherosclerosis: a micro-array study

Area of Science:

• Cardiovascular Biology
• Molecular Genetics
• Atherosclerosis Research

Background:

• Connexin37 (Cx37) regulates monocyte adhesion and protects against early atherosclerotic lesions.
• Cx37 expression is altered in atherosclerotic lesions, increasing in macrophages and decreasing in endothelium.
• Understanding Cx37's role in advanced atherosclerosis requires further molecular investigation.

Purpose of the Study:

• To investigate the molecular role of connexin37 (Cx37) in advanced atherosclerosis.
• To analyze global gene expression profiles in aortas of ApoE(-/-) and Cx37(-/-)ApoE(-/-) mice under diet-induced atherosclerosis.

Main Methods:

• Micro-array analysis for gene expression profiling in mouse aortas.
• Ingenuity Pathway Analysis (IPA) to identify biological pathways affected.
• Confirmation of gene expression changes at the protein level using (immuno-)histochemistry.

Main Results:

• Cx37 deficiency altered gene expression in young mice, favoring a pro-inflammatory phenotype.
• Diet-induced atherosclerosis further perturbed gene expression, impacting cell signaling, inflammation, vascular calcification, and matrix degradation.
• Significant differential expression of 106 genes before diet and 100 genes after diet was observed.

Conclusions:

• Cx37 deficiency shifts gene expression towards a pro-inflammatory state, influencing atherosclerosis progression.
• Cx37 plays a significant role in modulating gene expression related to vascular calcification and matrix degradation in advanced atherosclerosis.
• These findings provide novel insights into the molecular mechanisms underlying Cx37's involvement in plaque calcification.