Endothelial α1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endothelial Function

Background:

• Global alpha1AMPK deletion leads to endothelial dysfunction and vascular oxidative stress.
• Mechanisms may involve NOX-2 upregulation or phagocytic cell infiltration.
• Endothelial-specific deletion requires further investigation.

Purpose of the Study:

• To investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with endothelial-specific alpha1AMPK deletion.
• To elucidate the role of endothelial alpha1AMPK in regulating vascular oxidative stress and inflammation.

Main Methods:

• Generated endothelial-specific alpha1AMPK knockout mice by breeding floxed mice with Cre recombinase expressing mice (TekCre or Cadh5Cre).
• Administered chronic AngII infusion (0.5 mg/kg/day for 7 days) to wild-type and knockout mice.
• Assessed endothelial function, vascular oxidative stress markers (NOX-2, CD68), inflammatory cell infiltration (flow cytometry), and gene expression (MCP-1, CCL5, VCAM-1, HO-1).

Main Results:

• AngII infusion aggravated endothelial dysfunction in endothelial alpha1AMPK knockout mice compared to wild-type.
• Aortic NOX-2 and CD68 expression increased, indicating leukocyte infiltration.
• Increased abundance of T-cells, macrophages, and monocytes in knockout aortas.
• Enhanced expression of inflammatory chemokines and adhesion molecules in knockout mice.
• Blunted upregulation of heme oxygenase 1 (HO-1) in knockout mice, suggesting impaired antioxidant defense.

Conclusions:

• Endothelial alpha1AMPK limits inflammatory cell recruitment to the vessel wall.
• Endothelial alpha1AMPK maintains HO-1-mediated antioxidant defense.
• These mechanisms collectively reduce vascular oxidative damage and preserve endothelial function during AngII treatment.