ATP-Binding cassette transporter A1 modulates apolipoprotein A-I transcytosis through aortic endothelial cells

Area of Science:

• Cardiovascular Biology
• Lipoprotein Metabolism
• Endothelial Cell Biology

Background:

• High-density lipoproteins (HDL) and apolipoprotein A-I (apoA-I) exhibit atheroprotective effects, primarily within the arterial wall.
• HDL are the most abundant lipoproteins in the arterial intima, suggesting a critical role in vascular health.
• Recent findings indicate apoA-I transcytosis across aortic endothelial cells.

Purpose of the Study:

• To investigate the roles of ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) in apoA-I transcytosis.
• To determine how ABCA1 and SR-BI influence apoA-I binding, internalization, and transport through endothelial cells.

Main Methods:

• Utilized pharmacological interventions and RNA interference (RNAi) to modulate ABCA1 and SR-BI expression and function.
• Assessed apoA-I binding, internalization, and transcytosis in endothelial cells under various experimental conditions.
• Monitored endothelial cell monolayer integrity using inulin permeability assays and examined intracellular localization via fluorescence microscopy.

Main Results:

• Upregulating ABCA1 increased apoA-I binding and internalization; inhibiting ABCA1 function reduced these processes.
• Silencing ABCA1 significantly decreased apoA-I binding, internalization, and transcytosis by over 50%.
• Knocking down SR-BI had no significant effect on apoA-I transport, and endothelial cell integrity remained intact.

Conclusions:

• ATP-binding cassette transporter A1 (ABCA1), not scavenger receptor BI (SR-BI), plays a critical role in modulating apolipoprotein A-I (apoA-I) transcytosis across endothelial cells.
• ABCA1 mediates the binding and internalization of apoA-I, facilitating its passage through the endothelial barrier.
• These findings highlight ABCA1 as a key regulator of apoA-I transport within the arterial wall, relevant to atheroprotection.