Low-density-lipoprotein metabolism in type II hyperlipoproteinaemia.
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Apolipoproteins↗
Biomedical subjects
C J Packard
Publications and source records attributed to C J Packard.
Diagnosis of type III hyperlipoproteinemia by chromatography of plasma lipoproteins on columns containing agarose.
Agarose column chromatography has been used to separate plasma lipoproteins into very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Applied to the diagnosis of primary type III hyperlipoproteinemia, the procedure is capable of demonstrating three characteristic and specific changes from normality in the elution pattern of lipoproteins from patients with this condition. In the type III profile there is (a) incomplete separation of VLDL from putative LDL material, (b) early elution of the type III LDL with respect to a normal LDL marker, and (c) relative deficiency of type III LDL with elution characteristics of normal LDL. We advocate the use of this method in the diagnosis of type III hyperlipoproteinemia.
Adult↗
Atherogenic lipoprotein phenotype in type 2 diabetes: reversal with micronised fenofibrate.
BACKGROUND: To assess the short-term effects of a micronised formulation of fenofibrate on lipids, lipoproteins and their composition, reflecting an atherogenic lipoprotein phenotype (ALP), in patients with stable Type 2 diabetes. METHODS: Thirty-two (18 male, 14 female) patients with Type 2 diabetes were randomised to a double-blind, placebo-controlled parallel group study after a 4-week diet run-in phase to a 12-week treatment period with either daily micronised fenofibrate 200 mg (Lipantil Micro((R))) or placebo. RESULTS: Baseline mean lipid and lipoproteins were similar in both groups: total cholesterol (TC) 7.5 mmol/l, serum triglyceride (TG) 3. 1 mmol/l, HDL-cholesterol (HDL-c) 1.2 mmol/l, LDL-cholesterol (LDL-c) 4.7 mmol/l, and a predominance (52%) of small dense LDL-III at concentration of 192 mg lipoprotein/100 ml, reflecting an ALP. Treatment with micronised fenofibrate resulted in significant changes in TC (-17%, p<0.001), serum TG (-44%, p<0.05), HDL-c (+20%, p<0.01), LDL-c (-22%, p<0.001), apo-B (-18%, p<0.05) and alterations in LDL subfraction masses (LDL-I +64%, p<0.05; LDL-II +53%, p<0.05; LDL-III -51%, p<0.001) resulting in LDL-III comprising 28% of total LDL (p<0.001). In the placebo group the only significant changes were in TG (+21%, p<0.05) and apo-B (+9%, p<0.05). CONCLUSIONS: Micronised fenofibrate therapy in patients with Type 2 diabetes improved an establisheded ALP resulting in a more favourable lipid and LDL subfraction profile. The long-term clinical implications of these changes await the results of the major intervention trials of lipid modification in Type 2 diabetes.
Adult↗
Contribution of the receptor pathway to low density lipoprotein catabolism in humans. New methods for quantitation.
Receptor-mediated catabolism of low density lipoprotein (LDL) by cultured cells depends on the presence of functionally significant arginine and lysine residues on the lipoprotein apoprotein. When these are blocked, the recognition process is abolished, and catabolism of the modified lipoprotein is restricted to other mechanisms. Accurate discrimination between the activities of the receptor and nonreceptor pathways in vivo depends critically on the metabolic properties of this chemically modified lipoprotein. Here we report our experiences with two lysine-modified LDL tracers, glucosylated LDL (GLC-LDL) and 2-hydroxyacetaldehyde-treated LDL (HOET-LDL). The fractional clearance rate of GLC-LDL (0.25 +/- 0.05 pools/day, n = 5) was 50% of that of control material (0.51 +/- 0.09 pools/day) injected simultaneously into normal subjects. The HOET-LDL was also retarded in its clearance. Here, however, the fractional clearances of the control (0.37 +/- 0.06 pools/day, n = 6) and modified lipoprotein (0.19 +/- 0.03 pools/day) were lower than those obtained by the glucosylation procedure. We suspect that the prolonged incubation required for glucosylation of LDL artifactually accelerated its catabolism. The HOET-LDL does not suffer from this defect and seems to be a better tracer of the receptor-independent pathway. In a group of 10 subjects, HOET-LDL was metabolically indistinguishable from 1,2 cyclohexanedione-treated, arginine-modified LDL.
Acetaldehyde↗
Fenofibrate reduces low density lipoprotein catabolism in hypertriglyceridemic subjects.
This study examines the kinetic basis for the increment in plasma low density lipoprotein (LDL) levels that accompanies the fenofibrate treatment of severely hypertriglyceridemic (HTG) patients. Seven HTG men with a mean plasma triglyceride level of 1470 mg/dl were treated for 6 weeks. During treatment, their plasma triglyceride level fell by 77% and their cholesterol level by 41%. The fall in very low density lipoprotein (VLDL) cholesterol level was reciprocated by increments in the cholesterol level in both LDL and high density lipoproteins (HDL); the rise in HDL was confined to HDL3. LDL catabolism was examined before and during therapy using native and chemically modified tracers in an attempt to distinguish receptor-mediated from non-receptor-mediated clearance. In their basal state, the hypertriglyceridemic subjects overcatabolized both the native and the modified lipoprotein, implying that the non-receptor pathways were hyperactive. The mean fractional clearance rate of LDL via the receptor pathway was not significantly different from normal. Fenofibrate therapy corrected the patients' hypercatabolism, reducing the receptor-independent fractional clearance of apo LDL by 50% (from 0.48 to 0.24 pools/day; p less than 0.05). The mean fractional catabolic activity of the receptor route did not change, but when the increment in the plasma apo LDL concentration was taken into account, it was clear that the drug treatment was associated with an increase in the net amount cleared by the receptor pathway and with a reduction of lipoprotein uptake into receptor-independent routes.
Adult↗
Educating children about heart disease.
The authors have designed a computer-based health education programme introducing coronary heart disease (CHD) prevention to primary school children using the novel authoring system, Course Builder. To aid design of the programme, the basic knowledge of a randomly selected group of 90 children aged 8-11 years old from three city schools was assessed, using a questionnaire in storyline format. This surveyed children's understanding of the heart's basic function, the importance and prevalence of CHD, and perception of CHD as a preventable disease. The children's response after using the programme and their increased knowledge and awareness were evaluated, and the programme was deemed an overwhelming success.
Child↗
Affairs of the heart: cholesterol and coronary heart disease risk.
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Blood Chemical Analysis↗
Lipoprotein metabolism in familial hypercholesterolemia.
Low density lipoprotein (LDL) receptor deficiency, which causes homozygous familial hypercholesterolemia (FH), is accompanied by a gross disturbance in the metabolism of apolipoprotein (apo) B-containing lipoproteins. Not only is plasma LDL increased, but also the less dense lipoproteins (of very low and intermediate density) accumulate to a similar extent. Only the largest triglyceride-rich subfraction of very low density lipoprotein (VLDL) is not affected. The metabolic disturbance is characterized by oversynthesis of apo B and a defect in its clearance along the length of the delipidation cascade from VLDL to LDL. This phenomenon leads to delayed transit of particles through the system, extending the residence time of the B protein in the plasma by three- to fourfold. Receptor deficiency, therefore, results in accumulation of a number of lipoprotein species that have been implicated in the pathogenesis of atherosclerosis.
Humans↗