Cholesterol transport system: An integrated cholesterol transport model involved in atherosclerosis

Atherosclerosis, the pathological basis of most cardiovascular disease (CVD), is closely associated with cholesterol accumulation in the arterial intima. Excessive cholesterol is removed by the reverse cholesterol transport (RCT) pathway, representing a major antiatherogenic mechanism. In addition to the RCT, other pathways are required for maintaining the whole-body cholesterol homeostasis. Thus, we propose a working model of integrated cholesterol transport, termed the cholesterol transport system (CTS), to describe body cholesterol metabolism. The novel model not only involves the classical view of RCT but also contains other steps, such as cholesterol absorption in the small intestine, low-density lipoprotein uptake by the liver, and transintestinal cholesterol excretion. Extensive studies have shown that dysfunctional CTS is one of the major causes for hypercholesterolemia and atherosclerosis. Currently, several drugs are available to improve the CTS efficiently. There are also several therapeutic approaches that have entered into clinical trials and shown considerable promise for decreasing the risk of CVD. In recent years, a variety of novel findings reveal the molecular mechanisms for the CTS and its role in the development of atherosclerosis, thereby providing novel insights into the understanding of whole-body cholesterol transport and metabolism. In this review, we summarize the latest advances in this area with an emphasis on the therapeutic potential of targeting the CTS in CVD patients.