ABCA1 and Inflammation

ATP-binding cassette transporter subfamily A member 1 (ABCA1) is a plasma membrane protein well known for its role in regulating cellular cholesterol efflux and high-density lipoprotein (HDL) formation.1 Carriers of loss-of-function mutations in ABCA1 are characterized by reduced HDL cholesterol levels, which are nearly absent in the rare homozygous state (Tangier disease), and accumulation of cholesterol in several tissues, especially those rich in macrophages and reticuloendothelial cells.2 Although patients with Tangier disease rarely manifest with premature coronary artery disease, carriers of functional mutations in ABCA1 are characterized by decreased cholesterol efflux from fibroblasts and increased carotid wall thickness when compared with control subjects.3,4See accompanying article on page 1663 Cholesterol efflux from macrophages has been shown to be predictive of cardiovascular events and their incidence.5,6 ABCA1 is generally considered atheroprotective for its ability to meditate this first step of the reverse cholesterol transport pathway.7Figure. Potential mechanisms underlying increased inflammatory status in ATP-binding cassette transporter subfamily A member 1 (ABCA1)–deficient subjects. A , ABCA1 plays a major role in nascent high-density lipoprotein (HDL) formation and cellular cholesterol homeostasis. Excess free cholesterol (FC) and phospholipid in peripheral tissues, including macrophages in the arterial wall, can be transported out of cells through active lipid efflux via transporters such as ABCA1 into HDL. Through this process ABCA1 can modulate the amount of FC present in the plasma membrane. ABCA1-mediated reduction in …