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Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein-B and apoprotein-AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein-E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.

1. The effects of two beta-adrenoreceptor blocking drugs, metoprolol and atenolol, on plasma lipoproteins were studied in thirty-four patients using a single-blind cross-over design, with a 10-day placebo washout period between drugs. 2. Compared with placebo values, neither metoprolol nor atenolol influenced total plasma cholesterol levels, while total plasma triglycerides increased slightly. 3. Low density lipoprotein protein level remained unaltered, while high density lipoprotein (HDL) cholesterol and protein were significantly reduced by both beta-adrenoreceptor blockers. 4. The ratio of total cholesterol to HDL cholesterol was increased by both drugs. 5. The data suggest that patients taking these drugs over many years may be exposing themselves to increased vascular risk, despite other anticipated benefits from such therapy.

Apolipoproteins C-II (apoC-II) and C-III (apoC-III) are distributed among all the major lipoprotein classes, particularly very low density (VLDL) and high density lipoproteins (HDL). We have determined concentrations of apoC-II and apoC-III in VLDL and HDL in subjects with a wide range of VLDL triglyceride and HDL cholesterol levels, and correlated these levels with fractional catabolic rates (FCR) of VLDL triglyceride and HDL apolipoprotein A-I (apoA-I). Both apoC-II and apoC-III levels increased in VLDL as VLDL apolipoprotein B (apoB) and triglyceride levels rose. The rate of rise of VLDL apoC-III, however, was approximately 3 times greater than that of apoC-II, and positive correlations were present between the ratio of VLDL apoC-III/apoC-II and both VLDL apoB (r = 0.59; P less than 0.01) and VLDL triglyceride (r = 0.70; P less than 0.005) levels. Univariate analysis demonstrated that the FCR for VLDL triglyceride was inversely related to the ratio of apoC-III/apoC-II in VLDL (r = -0.58; P less than 0.05), although this relationship was not significant in a multivariate analysis. In HDL, concentrations of apoC-III and apoA-I were correlated (r = 0.73; P less than 0.005) while no correlation was observed between apoC-II and apoA-I levels. Univariate analyses of HDL variables revealed inverse correlations between the concentration of apoC-III and the FCR for apoA-I (r = -0.67; P less than 0.005) and between the ratio of apoC-III/apoA-I and the FCR for apoA-I (r = -0.66; P less than 0.005). Multivariate analysis confirmed the latter relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein (apo) E-containing subfractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) have been described in normolipidemic and hyperlipidemic subjects. These lipoproteins exist, however, in the presence of large amounts of apo A-I- and apo B-containing lipoproteins so that it has been difficult to assess the independence of these apo E-containing subclasses from the major lipoprotein classes. The present study has approached this question by taking advantage of three hypolipidemic states in which one or more of the major apolipoproteins is deficient or absent. After separating lipoproteins from whole plasma by molecular sieve chromatography followed by radioimmunoassay of column fractions, we found that two subjects with abetalipoproteinemia had no apo E-containing lipoproteins the size of VLDL or IDL and all the plasma apo E was in a fraction of large HDL. Two subjects with Tangier disease and two with familial apo A-I/C-III deficiency had extremely low levels of HDL cholesterol and of apo A-I-containing lipoproteins. In spite of the absence of classical HDL, a major fraction of apo E-containing lipoproteins was reproducibly observed at the elution volume characteristic of large HDL and was identical to that found in normal subjects. These data thus suggest the existence of apo E-containing lipoproteins that are the size of HDL and are not dependent upon the presence of either apo B or apo A-I. While studies in normal subjects indicate that apo E is associated with other apolipoproteins in HDL, further investigations will be needed to determine the full composition of these apo E-containing lipoproteins in the lipoprotein-deficient patients described in this report.

Serum high-density-lipoprotein (HDL) cholesterol and apoprotein (apo) A concentrations were significantly reduced at the time of renal transplantation in 26 patients with chronic renal failure. In a prospective evaluation the behaviour of HDL concentrations after grafting was found to depend on renal function. Graft function was sustained in 19 patients, in whom HDL-cholesterol and apo A concentrations increased to lie within normal limits by six months after the operation. Successful transplantation also restored to normal the lipid and protein content of HDL as expressed by the ratio of HDL cholesterol to apo A. When transplant function was not sustained (seven patients), however, no changes in HDL were observed up to the time of the graft loss. Such changes in HDL with successful kidney grafting augur well in a population with many risk factors for coronary heart disease.

The hyperlipoproteinaemia accompanying chronic renal failure and renal transplantation has been re-examined in terms of the apoprotein (apo A and apo B) moieties of the high density (HDL) and low density (LDL) lipoproteins. Hypertriglyceridaemia is prevalent in chronic uraemia and is not corrected by haemodialysis or renal transplantation. Hypercholesterolaemia is characteristic only of renal allograft recipients. Apo A levels are reduced in undialyzed uraemic and remain low during haemodialysis, as well as in patients with renal allografts of less than six months duration. In renal transplant recipients of greater than one year duration, apo A levels are normalized. The normalization of apo A level is related to the stability of graft function, as determined by sequential analysis of 15 renal transplant recipients. Apo B levels are normal transplant recipients. Apo B levels are normal in uraemic and dialyzed patients, but are elevated in long term transplant recipients. Unlike apo A levels, this alteration does not appear to reflect the restoration of kidney function.