Structural and functional differences of subspecies of apoA-I-containing lipoprotein in patients with plasma cholesteryl ester transfer protein deficiency.

ApoA-I-containing lipoproteins exist in plasma in two main forms: one contains only apoA-I (LpA-I) while the other contains both apoA-I and apoA-II (LpA-I/A-II). We characterized structural and functional changes of these lipoproteins in six patients with cholesteryl ester transfer protein (CETP) deficiency. In these patients, the amount of LpA-I and LpA-I/A-II had increased significantly. Sixty-five percent of plasma apoA-I was associated with LpA-I/A-II, which indicated that LpA-I/A-II was predominant. The chemical composition of both LpA-I and LpA-I/A-II was characterized by increased ratios of neutral to polar lipid, compared with findings in normal subjects. Particle sizes of these lipoproteins shifted to larger diameter ranges, as compared to the size seen in normal subjects. Incubation of patients' LpA-I and LpA-I/A-II with CETP markedly corrected the chemical and physical abnormalities in these lipoproteins. Cholesterol-reducing capacities of these lipoproteins from macrophage foam cells were significantly lower than in normal controls. Cholesterol esterification rates in LpA-I, LpA-I/A-II, and plasma were significantly lower in patients than in normal controls. We propose that the structure and function of LpA-I and LpA-I/A-II are severely affected in the presence of CETP deficiency.

[1]  A. Tall,et al.  Gender effects on the distribution of the cholesteryl ester transfer protein in apolipoprotein A-I-defined lipoprotein subpopulations. , 1994, Journal of lipid research.

[2]  P. Duchateau,et al.  Biochemical characterization of the three major subclasses of lipoprotein A-I preparatively isolated from human plasma. , 1993, Biochemistry.

[3]  S. Eisenberg,et al.  High density lipoprotein metabolism. , 1984, Journal of lipid research.

[4]  R. Krauss,et al.  Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI , 1991, Nature.

[5]  N. Miller,et al.  Pathophysiology of reverse cholesterol transport. Insights from inherited disorders of lipoprotein metabolism. , 1989, Arteriosclerosis.

[6]  J. Albers,et al.  Distribution and localization of lecithin:cholesterol acyltransferase and cholesteryl ester transfer activity in A-I-containing lipoproteins. , 1986, Journal of lipid research.

[7]  W. Willett,et al.  A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. , 1991, The New England journal of medicine.

[8]  A. Tall,et al.  Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins , 1989, Nature.

[9]  A. von Eckardstein,et al.  Cell-derived unesterified cholesterol cycles between different HDLs and LDL for its effective esterification in plasma. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[10]  S. Yamashita,et al.  Small polydisperse low density lipoproteins in familial hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity. , 1988, Atherosclerosis.

[11]  S. Horiuchi,et al.  Isolation of apolipoprotein A-I-containing lipoproteins by immunoaffinity chromatography using a formylated derivative of cellulose gel. , 1989, Clinica chimica acta; international journal of clinical chemistry.

[12]  S. Eisenberg,et al.  Intravascular metabolism of the cholesteryl ester moiety of rat plasma lipoproteins. , 1984, Journal of lipid research.

[13]  T. Ohta,et al.  Studies on the lipid and apolipoprotein compositions of two species of apoA-I-containing lipoproteins in normolipidemic males and females. , 1988, Journal of lipid research.

[14]  S. Horiuchi,et al.  Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase. , 1992, Biochimica et biophysica acta.

[15]  K. Weber,et al.  The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. , 1969, The Journal of biological chemistry.

[16]  A. Albers,et al.  Comparison of improved precipitation methods for quantification of high-density lipoprotein cholesterol. , 1985, Clinical chemistry.

[17]  N. B. Myant,et al.  The distribution of cholesterol and apoprotein A-I between the lipoproteins in plasma and peripheral lymph from normal human subjects. , 1984, Atherosclerosis.

[18]  Y. Ikeda,et al.  LDL inhibits the mediation of cholesterol efflux from macrophage foam cells by apoA-I-containing lipoproteins. A putative mechanism for foam cell formation. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[19]  Ohta Takao,et al.  Lipid and apolipoprotein levels in patients with nephrotic syndrome. , 1981, Clinica chimica acta; international journal of clinical chemistry.

[20]  A. Tall,et al.  An interaction between the human cholesteryl ester transfer protein (CETP) and apolipoprotein A-I genes in transgenic mice results in a profound CETP-mediated depression of high density lipoprotein cholesterol levels. , 1992, The Journal of clinical investigation.

[21]  N. Miller.  Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis. , 1987, American heart journal.

[22]  Yves,et al.  Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism. , 1989, The Journal of clinical investigation.

[23]  J. Fruchart,et al.  Apolipoprotein A-I containing lipoproteins in coronary artery disease. , 1987, Atherosclerosis.

[24]  Y. Matsuzawa,et al.  Determination by the SRID Method of Normal Values of Serum Apolipoproteins (A-I, A-II, B, C-II, C-III, and E) in Normolipidemic Healthy Japanese Subjects , 1986 .

[25]  R. Morfin,et al.  Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. , 1970, Journal of lipid research.

[26]  C. Ashall,et al.  Compartmentalization of Water in Human Atherosclerotic Lesions: Changes in Distribution and Exclusion Volumes for Plasma Macromolecules , 1984, Arteriosclerosis.

[27]  W. J. Johnson,et al.  Mechanisms and consequences of cellular cholesterol exchange and transfer. , 1987, Biochimica et biophysica acta.

[28]  P. Barter,et al.  Lipoprotein substrates for plasma cholesterol esterification. Influence of particle size and composition of the high density lipoprotein subfraction 3. , 1985, Atherosclerosis.

[29]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[30]  D. Gordon,et al.  High-density lipoprotein--the clinical implications of recent studies. , 1989, The New England journal of medicine.

[31]  N. B. Myant,et al.  Further evidence for the role of high density lipoprotein in the removal of tissue cholesterol in vivo. , 1982, Atherosclerosis.

[32]  C. Fielding,et al.  Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin:cholesterol acyltransferase. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Heider,et al.  The picomole determination of free and total cholesterol in cells in culture. , 1978, Journal of Lipid Research.

[34]  D. Steinberg,et al.  Dissociation of tissue uptake of cholesterol ester from that of apoprotein A-I of rat plasma high density lipoprotein: selective delivery of cholesterol ester to liver, adrenal, and gonad. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[35]  D. B. Zilversmit,et al.  Purification and characterization of lipid transfer protein(s) from human lipoprotein-deficient plasma. , 1982, Journal of lipid research.

[36]  A. Tall.  Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. , 1990, The Journal of clinical investigation.

[37]  E. Rubin,et al.  Protein composition determines the anti-atherogenic properties of HDL in transgenic mice , 1993, Nature.

[38]  J. Frohlich,et al.  Detection of heterozygotes for familial lecithin: cholesterol acyltransferase (LCAT) deficiency. , 1982, American journal of human genetics.