Understanding the Regulation of “Reverse Cholesterol Transport ”at Molecular Level. An Interactive Comprehensive Appraisal.

                   An Interactive Comprehensive Appraisal.

     Large population studies conclusively demonstrated that plasma levels of high density lipoprotein cholesterol (HDL-C) as well as its major apolipoprotein constituent apolipoprotein A-I (apoA-I) are inversely associated with the risk of atherosclerotic cardiovascular disease.

      However, within these study populations there is still a substantial number of patients that experience complications of cardiovascular disease despite considerably high HDL-C plasma levels, and vice versa there are individuals with low plasma HDL-C levels that do not develop clinically significant atherosclerosis.

       Such observations lead to the investigation how HDL particles confer protection against atherosclerosis.

       One of the earliest recognized functions of HDL is that it promotes cholesterol efflux from macrophage foam cells, which constitute the hallmark cell type of atherosclerotic lesions.

       Importantly, cholesterol efflux from foam cells can revert this phenotype leading to macrophage regress from lesions and a subsequent reduction in lesion burden.       

       Subsequently, the cholesterol effluxed from foam cells towards HDL should ideally be irreversibly eliminated from the body to prevent re-uptake into the vessel wall.

       HDL-mediated cholesterol efflux therefore constitutes a key step not only for preventing lesion progression but also for clinical efforts to induce regression of preexisting atherosclerotic plaques.

     This goal is achieved by a complex multistep process that has been coined Reverse Cholesterol Transport (RCT).       

     The recent introduction of a surrogate method aiming at determining specifically RCT from the macrophage compartment has facilitated research on the different components and pathways relevant for RCT.

      An attempt has been made in this Booklet to provide a comprehensive overview of studies carried out on macrophage specific RCT including a quick reference guide of available data and summarize the knowledge and insights gained on the Regulation of the RCT Pathway.

      Further, a discussion of methodological issues as well as of the respective relevance of specific pathways for RCT is also included.

…Dr. H. K. Saboowala.

           M.B.(Bom) .M.R.S.H.(London)