Effects of Chronic Inflammatory Activation of Murine and Human Arterial Endothelial Cells at Normal Lipoprotein and...

Area of Science:

• Vascular Biology
• Molecular Biology
• Immunology

Background:

• Endothelial cell activation is vital for immunity but implicated in atherosclerosis.
• Previous work linked inflammatory stimulation with high lipoprotein levels to accelerated atherogenesis.

Purpose of the Study:

• To investigate aortic transcriptome changes due to chronic endothelial inflammation in mice at normal lipoprotein levels.
• To compare these changes with the inflammatory response in isolated endothelial cells in vitro.

Main Methods:

• Utilized a mouse model with constitutive active IκB kinase 2 (caIKK2) in arterial endothelial cells.
• Analyzed transcriptomic changes in whole aortas and isolated human endothelial cells.
• Performed pathway and network analyses.

Main Results:

• Upregulation of cell death and mitochondrial beta-oxidation pathways, predicting increased endothelial apoptosis and necrosis.
• Reduction in protein synthesis genes.
• Highest upregulated gene: ACE2 (angiotensin-converting enzyme 2).
• Isolated human endothelial cells showed reduced DNA replication and repair.

Conclusions:

• Chronic endothelial inflammation, independent of high lipoprotein levels, alters aortic gene expression.
• This inflammation promotes endothelial dysfunction through increased cell death and impaired repair mechanisms.
• Findings highlight the significant role of inflammation in atherogenesis and endothelial health.