Gram-negative bacteria activate cellular pathways in plaque microenvironment; Systems biology approach

Area of Science:

• Vascular Biology
• Immunology
• Microbiology

Background:

• Inflammatory events and bacterial infections are linked to atherosclerosis.
• Gram-negative bacterial infections impact endothelial cells (ECs), macrophages (MQs), vascular smooth muscle cells (VSMCs), and dendritic cells (DCs).

Purpose of the Study:

• To investigate signaling and metabolic pathways in vascular cells upon Gram-negative bacterial infection.
• To explore pathway cross-talk and enrichment in cellular and plaque networks.

Main Methods:

• Analysis of high-throughput expression data from public repositories (GEO, MAT).
• Identification of upregulated differentially expressed genes (DEGs) using R software.
• Pathway identification via Enricher/Reactome and network visualization with Cytoscape.

Main Results:

• Activated pathways include Cytokines, INF, GPCR, and NOTCH in various vascular cells (ECs, MQs, VSMCs, DCs).
• Netrin-1 and EGFR pathways were activated in intimal thick/xanthoma plaques.
• Innate and adaptive immune system pathways were activated in fibrous cap atheroma plaques.

Conclusions:

• Gram-negative bacterial infections induce specific signaling pathway activation in the vascular microenvironment.
• Cellular cross-talks exacerbate these pathways, contributing to unstable plaque development.