TANGIER DISEASE - ISOLATION AND CHARACTERIZATION OF LPA-I, LPA-II, LPA-I-A-II AND LPA-IV PARTICLES FROM PLASMA

Tangier disease (TD) is characterized by extremely low plasma levels o f HDL, apoA-I and apoA-II due to very rapid catabolism. However, the r isk of premature coronary heart disease (CHD) is not markedly increase d in TD. In order to gain insight into reverse cholesterol transport i n TD, we isolated LpA-I, LpA-I:A-II, LpA-II and LpA-IV particles from fasting plasma of 5 TD patients. LpA-I composition was similar to cont rol LpA-I, but TD LpA-I had more LCAT and CETP activity (respectively, 0.35 +/- 0.14 and 0.14 +/- 0.04 mumol of cholesterol esterified/h/mug of protein, and 7 +/- 2.5 and 1.4 +/- 0.3 mumol of cholesteryl ester transferred/h/mug of protein). In contrast, TD LpA-I:A-II had abnormal composition, with a low molar ratio of apoA-I to apoA-II (0.2-1.33). In addition, LpA-I:A-II in TD contained a substantial amount of apoA-I V compared with control, making this particle an LpA-I:A-II:A-IV compl ex. LpA-I:A-II from normal plasma do not promote cholesterol efflux fr om adipocytes cells, whereas TD LpA-I:A-II:A-IV complexes promoted cho lesterol efflux from these cells. Moreover LpA-I:A-II:A-IV complexes h ave more LCAT and CETP activity than control (respectively 1.2 +/- 0.1 6 and 0.05 +/- 0.01 mumol of cholesterol esterified/h/mug of protein a nd, 41 +/- 3.7 and 1 +/- 0.4 mumol of cholesteryl ester transferred/h/ mug of protein). The LpA-II particle in TD represented in fact an LpA- II:A-IV complex (75% mol apoA-II and 22% mol apoA-IV). This particle d id not promote cholesterol efflux, but LCAT and CETP activity were pre sent. LpA-IV particles had the capacity to promote cholesterol efflux and had both LCAT and CETP activity. LpA-IV may contribute to maintain the reverse cholesterol transport in TD. Our results indicate the pot ential importance of apoA-IV in maintaining reverse cholesterol transp ort in TD. In spite of the low steady state HDL-cholesterol levels in TD, LpA-I, LpA-I:A-II:A-IV complex and LpA-IV appear to be active in r everse cholesterol transport and may help to prevent premature CHD in TD.