Abstract
High-density lipoproteins (HDLs) protect against cardiovascular disease by removing cholesterol from arterial macrophages. One important pathway involves HDL apolipoproteins, which remove cellular cholesterol and phospholipids by an active process mediated by a cell membrane protein termed ATP-binding cassette transporter (ABC)A1. The interaction of apolipoproteins with ABCA1-expressing cells elicits several biological responses that coordinate removal of cellular lipids, including solubilizing membrane lipid domains, stabilizing ABCA1 protein and transducing signals. The apolipoprotein structural determinant responsible for all these activities is the amphipathic α-helix. Human and animal studies have shown that a reduced apolipoprotein supply and impaired macrophage ABCA1 activity are atherogenic. Metabolic factors associated with diabetes, the metabolic syndrome and inflammation can damage apolipoproteins and ABCA1, raising the possibility that impaired cholesterol removal from arterial cells contribut...
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