ATP-binding cassette B8 prevents endothelial dysfunction and atherosclerosis

Area of Science:

• Cardiovascular Biology
• Mitochondrial Function
• Vascular Homeostasis

Background:

• ATP-binding cassette B8 (ABCB8) exports iron from mitochondria, preventing oxidative stress.
• The specific role of ABCB8 in endothelial and vascular function is not well understood.

Purpose of the Study:

• To elucidate the function of ABCB8 in endothelial cells and its impact on vascular homeostasis.
• To investigate the molecular mechanisms linking ABCB8, iron, and vascular inflammation.

Main Methods:

• Utilized endothelial-specific inducible Abcb8 knockout mice (Abcb8^ECKO).
• Conducted intravital imaging and ex vivo aortic treatments with iron chelators and TGF-β inhibitors.
• Analyzed transcriptional changes in various vascular and immune cells.

Main Results:

• Loss of ABCB8 in endothelial cells activates a pro-inflammatory program, upregulating TGF-β signaling.
• TGF-β acts as an iron effector, increasing mitochondrial ROS and damage.
• Abcb8^ECKO mice exhibit enhanced vascular inflammation, atherosclerosis, and hypertension.

Conclusions:

• Identified a novel ABCB8-iron-TGF-β axis regulating endothelial cell function and vascular inflammation.
• ABCB8 plays a critical atheroprotective role by suppressing iron-dependent vascular inflammation.
• ABCB8 represents a potential therapeutic target for vascular diseases.