DYSFUNCTIONAL HIGH-DENSITY LIPOPROTEINS: ROLE IN ATHEROGENESIS AND POTENTIAL TARGETS FOR PHOSPHOLIPID THERAPY

摘要

In recent years the number of articles on damages of high-density lipoproteins (HDL) properties in patients with atherosclerosis has sharply increased. First, it concerns their ability to accept cholesterol (CH) from macrophages - the basis of antiatherogenic action of HDL. This ability was assessed ex vivo - by activity of cell cholesterol (CH) efflux to HDL or into patient's serum. In many works inverse relationship was shown between CH acceptor capacity of HDL and severity of atherosclerotic disease or frequency of its exacerbations during long-term observation, independent from HDL CH concentration. This led to the emergence of the concept of importance of "not only HDL quantity but also of their quality", i. e. functionality. In this review we consider pathways of cellular CH efflux (mainly mediated by cell proteins), methods used for detection of dysfunctional HDL, and results of relevant studies in various categories of patients. These studies directed to identification of mechanisms of damages of HDL properties by means of analysis of their composition, used various approaches including those of proteomics and lipidomics. However, now there are no proven targets for correction of HDL dysfunctionality. The only factor, that is underlined by many authors, is the significance of HDL phospholipids, which level correlates with activity of cellular CH efflux. This allows to take a fresh look at previously used phospholipid therapy of atherosclerosis. Its mechanism is apparently not lowering of plasma CH, as was previously expected, but the improvement of HDL antiatherogenic properties. For its practical usage it is necessary to elaborate principally novel formulations with high bioavailability of phospholipids - for HDL enrichment by phospholipid and thereby normalization of their ability to remove CH from tissues.