Ht31, a Protein Kinase A Anchoring Inhibitor, Induces Robust Cholesterol Efflux and Reverses Macrophage Foam Cell Formation through ATP-binding Cassette Transporter A1

摘要: Macrophage foam cell is the predominant type in atherosclerotic lesions. Removal of excess cholesterol from macrophages thus offers effective protection against atherosclerosis. Here we report that a protein kinase A (PKA)-anchoring inhibitor, st-Ht31, induces robust cholesterol/phospholipid efflux, and ATP-binding cassette transporter A1 (ABCA1) greatly facilitates this process. Remarkably, found st-Ht31 completely reverses formation, process ABCA1-dependent. The reversal also accompanied by restoration well modulated inflammatory response to LPS. There no detectable toxicity associated with even when cells export up 20% cellular per hour. Using FRET-based PKA biosensors live cells, provide evidence drives efflux elevating activity specifically cytoplasm. Furthermore, ABCA1 uptake. This allows effectively remove ABCA1-expressing cells. We speculate de-anchoring novel therapeutic strategy lipid-laden lesion macrophages.