HIGH-DENSITY-LIPOPROTEINS AND REVERSE CHOLESTEROL TRANSPORT - LESSONSFROM MUTATIONS

High density lipoproteins (HDL) encompass structurally and functionall y heterogeneous particles. Two-dimensional nondenaturing polyacrylamid e gradient gel electrophoresis (2D-PAGGE) and subsequent immunoblottin g helps to differentiate quantitatively minor HDL-subclasses from the bulk of HDL, which contains apo A-I and has electrophoretic alpha-mobi lity. Pulse-chase experiments identified the quantitatively minor HDL subclasses pre beta(1)-LpA-I, gamma-LpE and LpA-IV as initial and fast accepters of cell-derived cholesterol and alpha-migrating HDL (i.e, a lpha-LpA-I) as a late and slow acceptor. In plasmas of patients with c ertain forms of familial HDL-deficiency such as apo A-I deficiency and Tangier disease, pre beta(1)-LpA-I, gamma-LpE and LpA-IV represent th e only HDL particles and account for the significant residual choleste rol efflux capacity of these plasmas. These particles, however, also f ulfill important roles in reverse cholesterol transport of normal plas ma. Pre beta(1)-LpA-I, for example, is generated, during the interconv ersion of HDL by lipid transfer proteins. Thus, incubation of plasma w ith phospholipid transfer protein increases the concentration of pre b eta(1)-LpA-I and in parallel increases the cholesterol efflux capacity of plasma indicating that lipid transfer proteins modulate cholestero l efflux by modification of HDL subclass composition. Apo E and gamma- LpE are of special interest for reverse cholesterol transport since ma crophages can produce apo E. (C) 1998 Elsevier Science Ireland Ltd. Al l rights reserved.