HDL and reverse cholesterol transport in humans and animals: Lessons from pre-clinical models and clinical studies

The ability to accept cholesterol from cells and to promote reverse cholesterol transport (RCT) represents the best characterized antiatherogenic function of HDL. Studies carried out in animal models have unraveled the multiple mechanisms by which these lipoproteins drive cholesterol efflux from macrophages and cholesterol uptake to the liver. Moreover, the influence of HDL composition and the role of lipid transporters have been clarified by using suitable transgenic models or through experimental design employing pharmacological or nutritional interventions. Cholesterol efflux capacity (CEC), an in vitro assay developed to offer a measure of the first step of RCT, has been shown to associate with cardiovascular risk in several human cohorts, supporting the atheroprotective role of RCT in humans as well. However, negative data in other cohorts have raised concerns on the validity of this biomarker. In this review we will present the most relevant data documenting the role of HDL in RCT, as assessed in classical or innovative methodological approaches.