ABC transporters: lipid transport and inflammation

摘要

Atherosclerosis is a chronic inflammatory disease induced in part by disorders of lipid homeostasis. In recent years a growing body of work has shed light on the connection between lipid metabolism and inflammation. Central to this connection appears to be the ABC family of lipid transporters and the LXR nuclear receptors that regulate their transcription. One of the main functions of the ABC transporters ABCA1 and ABCG1 is to carry out reverse cholesterol transport. In this process, cholesterol is removed from peripheral cells such as macrophages to apolipoprotein A-I by the action of ABCA1 or to HDL by the action of ABCG1, and delivered to the liver for excretion as bile acids. By this mechanism, ABCA1 and ABCG1 help to regulate cholesterol homeostasis [1], Vaughan and Oram [2] have shown that this process occurs sequentially, when apoA-I particles that have been lipi-dated by ABCA1 expressing cells are then able to act as acceptors of cholesterol from cells expressing ABCG1. Cholesterol products act as regulators of expression of these transporters through LXR. Cholesterol loading of cells leads to the generation of oxysterol ligands of LXR, which results in increased expression of ABCA1 and G1 to mediate removal of cholesterol from the cells [3].