Homocyst(e)ine and coronary artery disease. Clinical evidence and genetic and metabolic background.

Many studies have demonstrated a strong association between elevated plasma total homocyst(e)ine levels and vascular diseases. Consequently, hyperhomocyst(e)inemia is now generally accepted as an independent risk factor for coronary artery disease. We critically reviewed the results of 35 human studies in which the levels of plasma total homocysteine were measured in patients with atherosclerotic diseases (n = 4338) and in controls (n = 22,593).

Effect of lipoprotein-X on lipid metabolism in rat kidney.

Lipoprotein-X (Lp-X) is found in the plasma of patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. The majority of the patients with this disorder develop progressive glomerulosclerosis. In this study, the effect of Lp-X on lipid metabolism in perfused rat kidney was investigated.

The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes.

Lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes represent a group of rare genetic disorders of HDL metabolism that have been the subject of a large number of clinical, biochemical, and genetic studies. Of special interest are patients with LCAT-related disorders with severe HDL deficiency and the apparent absence of premature atherosclerosis. This finding is inconsistent with the general concept that low HDL cholesterol levels are an obligate risk factor for atherosclerosis.

"Tall oil"-derived phytosterols reduce atherosclerosis in ApoE-deficient mice.

We investigated the effects of a "tall oil"-derived phytosterol mixture (TODPM) on the formation of atherosclerotic lesions in apoE-deficient mice. TODPM was added at 2% (wt/wt) to the chow of nine mice; the control group had six animals. The diet of all animals contained 9% (wt/wt) fat and 0.

Stability of nonrelativistic quantum mechanical matter coupled to the (ultraviolet cutoff) radiation field.

We announce a proof of H-stability for the quantized radiation field, with ultraviolet cutoff, coupled to arbitrarily many non-relativistic quantized electrons and static nuclei. Our result holds for arbitrary atomic numbers and fine structure constant. We also announce bounds for the energy of many electrons and nuclei in a classical vector potential and for the eigenvalue sum of a one-electron Pauli Hamiltonian with magnetic field.

The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).

Aims: To clarify the underlying causes of corneal opacification in Tangier disease.

Methods: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry.

Results: Membranous inclusions in the stroma were seen on transmission electron microscopy.

Effects of alcohol on plasma lipoprotein metabolism.

Alcohol consumption affects a number of steps in plasma lipoprotein metabolism: it serves as a substrate for lipoprotein triglyceride synthesis, alters synthesis of apolipoproteins, and affects the activity of the key enzymes of lipoprotein metabolism, namely lipoprotein lipase and hepatic lipase, and cholesterol ester transfer protein. In addition, alcohol consumption may increase tissue sensitivity to insulin. The specific effects of alcohol consumption vary and depend on the amount ingested, type of drinking (as opposed to moderate regular alcohol consumption, binge drinking results in an unfavourable serum lipoprotein profile), body composition of the drinkers and a number of gene/environment interactions.

Measurement of fractional esterification rate of cholesterol in plasma depleted of apoprotein B containing lipoprotein: methods and normal values.

The distribution of differently sized HDL particles in the plasma can be assessed by measurement of the fractional rate of cholesterol esterification (FERHDL). We have characterized the isotopic assay and compared it to the enzymatic measurement of the decrease in HDL free cholesterol (mass assay). The normal values of FERHDL were established in 116 apparently healthy individuals.

Cholesterol and atherosclerotic vascular disease: from science to public health policy.

Advances in our understanding of the pathology, epidemiology, genetics (particularly the recent research on transgenic animals) and the results of randomized prospective clinical trials all contribute to the formation of public health policy on serum cholesterol and other lipids. This article outlines the scientific background of these policies. There remains little doubt that dyslipidemia contributes to the development of coronary atherosclerosis and that effective treatment can prevent or retard its development.

Relation of cholesterol esterification rate to the plasma distribution of high-density lipoprotein subclasses in normal and hypertensive women.

We studied the particle size distribution of plasma high-density lipoproteins (HDL) by gradient gel electrophoresis and by assay of cholesterol esterification rate (FERHDL) in plasma depleted of very low (VLDL) and low-density (LDL) lipoproteins in 32 hypertensive women (53 +/- 10 y old) and in an age-matched group of 21 apparently healthy women. There were no significant differences between the groups with respect to their plasma total, HDL- and LDL-cholesterol. The plasma triglyceride (TG) concentration was significantly higher in the group of hypertensive women, and HDL-free cholesterol was significantly lower in the hypertensive group.

Role of lecithin:cholesterol acyltransferase and apolipoprotein A-I in cholesterol esterification in lipoprotein-X in vitro.

Lipoprotein-X (Lp-X) is an abnormal particle present in the plasma of patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes or cholestatic liver disease. Compared to other lipoproteins, Lp-X contains a high content of unesterified cholesterol (30%, w/w) to phosphatidylcholine (60%, w/w). The objective of this study was to evaluate the role of LCAT and apolipoprotein A-I (apoA-I) in Lp-X metabolism in vitro and to elucidate the regulation of cholesterol esterification in this unique lipoprotein.

Hydrocephalus, mineralizing angiopathy, hypercholesterolemia, and hyperlipoprotein (a).

A boy born at 34 weeks gestation with initially normal development presented with acute hydrocephalus at 22 months. Subsequently his development has been slow and complicated clinically by epilepsy. Upon extensive investigation, he has been found to have extremely elevated lipoprotein(a) levels, hypercholesterolemia (familial), and lesions of the cortex and meninges.

Patients with apoE3 deficiency (E2/2, E3/2, and E4/2) who manifest with hyperlipidemia have increased frequency of an Asn 291-->Ser mutation in the human LPL gene.

Approximately 1% to 2% of persons in the general population are homozygous for a lipoprotein receptor-binding defective form of apoE (apoE2/2). However, only a small percentage (2% to 5%) of all apoE2/2 homozygotes develop type III hyperlipoproteinemia. Interaction with other genetic and environmental factors are required for the expression of this lipid abnormality.

Severe familial HDL deficiency in French-Canadian kindreds. Clinical, biochemical, and molecular characterization.

A decreased level of HDL cholesterol (HDL-C) is the most common lipoprotein abnormality seen in people with premature coronary artery disease (CAD). In many cases, HDL-C reduction in patients with CAD may be the result of increased apo B-containing lipoprotein production by the liver with secondary hypoalphalipoproteinemia. Primary hypoalphalipoproteinemia is seen in approximately 4% of people with CAD.

Lipoproteins and homocyst(e)ine as risk factors for atherosclerosis: assessment and treatment.

Two new important independent risk factors for coronary artery disease (CAD) have been identified: lipoprotein (a) [Lp(a)] and homocyst(e)ine. Both are associated with increased frequency of cardiovascular events, both coronary and peripheral. Measurement of these two factors should be considered in patients with symptomatic CAD, stroke, a strong family history (but low other conventional risk factors); in first degree relatives of those with very high Lp(a) or homocyst(e)ine levels; and in other individuals in whom the need for an aggressive treatment of metabolic risk factors is indicated.

Characterization of subspecies of lipoprotein containing apolipoprotein A-I in heterozygotes for familial lecithin:cholesterol acyltransferase deficiency.

We characterized two species of lipoproteins containing apo A-I, one containing only apo A-I (LpA-I) and the other containing both apo A-I and apo A-II (LpA-I/A-II), in three heterozygotes for familial lecithin:cholesterol acyltransferase deficiency (LCAT). In these patients, particle size and the chemical composition of LpA-I differed from those in normal controls. Small particles < 8.

Lp(a) concentration and apo(a) isoform size. Relation to the presence of coronary artery disease in familial hypercholesterolemia.

We studied the relation between the concentration of lipoprotein(a) [Lp(a)] in plasma, apolipoprotein (a) [apo(a)] phenotype, and the clinical expression of coronary artery disease (CAD) in a previously described cohort of patients with familial hypercholesterolemia (FH) and an appropriate population of control subjects. The plasma concentration of Lp(a) was markedly skewed in both the FH and control populations; however, the distribution was less skewed in FH (50% greater than 300 mg/L) compared with control subjects (27% greater than 300 mg/L). Patients with FH had significantly higher median and mean log Lp(a) levels compared with control subjects.

Evidence for impaired cellular cholesterol removal mediated by apo A-I containing lipoproteins in patients with familial lecithin: cholesterol acyltransferase deficiency.

We investigated the cholesterol reducing capacity of two species of lipoproteins containing apo A-I, one containing only apo A-I (LpA-I) and the other containing apo A-I and apo A-II (LpA-I/A-II), in 7 patients (4 homozygotes and 3 heterozygotes) with familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Interaction of normal LpA-I or LpA-I/A-II with macrophage foam cells induced a mass reduction in cholesterol from these cells and the cholesterol reducing capacity of LpA-I was greater than that of LpA-I/A-II. When foam cells were incubated with these lipoproteins from homozygotes or heterozygotes, the capacity of LpA-I and LpA-I/A-II particles to reduce cellular cholesterol was decreased by approx.

Structural and functional assessment of high-density lipoprotein heterogeneity.

We studied the heterogeneity of high-density lipoproteins (HDL) in plasma of 110 subjects, using three different methods: (a) gradient gel electrophoresis (GGE); (b) electroimmunoassay, to measure the concentration of lipoprotein particles containing apoprotein (apo) AI but no apo-AII (LP AI); and (c) cholesterol esterification rate (FERHDL) in very-low- and low-density lipoprotein-depleted plasma. There were two study groups: patients with hypertension, whose plasma lipid profile was similar to their respective controls, and patients with hypoalphalipoproteinemia (hypoalpha), whose family members served as controls. Values for FERHDL were significantly higher in both risk groups than in their respective controls.