Search PubMed⌕ Search

Biomedical subjects

J Davignon

Publications and source records attributed to J Davignon.

At least 73 records · Page 4Linked to original sources
PubMed1996

Triglycerides: a risk factor for coronary heart disease.

Multiviriate analysis of epidemiological data has often shown that elevated plasma triglyceride (TG) concentration is not an independent risk factor for coronary heart disease (CHD). However, more recently, subgroup- and meta-analyses have supported an independent association between TG and CHD. The strength of TG to predict the CHD lies in its ability to reflect the presence of atherogenic plasma TG-rich lipoprotein (TRL) remnants. Clinical evidence for the potential atherogenicity of TRL is provided by patients with type III hyperlipoproteinaemia, hepatic lipase deficiency or apolipoprotein E deficiency, who have marked increase in plasma remnant lipoproteins and an increased incidence of CHD. Indirect evidence suggests that the presence of a single epsilon 2 allele may have atherogenic potential by influencing plasma remnant accumulation in the presence of a second environmental or genetic factor. Recent studies have also indicated that the magnitude of postprandial triglyceridaemia is a significant predictor of CHD. Emerging data from angiographic intervention trials have implicated TRL in atherosclerotic disease progression independently of low-density lipoproteins (LDL). Thus, in hypertriglyceridaemic patients, physicians should conduct a thorough clinical evaluation, a family survey, an assessment of associated risk factors and a complete analysis of the plasma lipoprotein profile, in order to assess the atherogenic potential of this hyperlipidaemia.

Animals↗
PubMed1996

Apolipoprotein E and low-density lipoprotein binding and internalization in primary cultures of rat astrocytes: isoform-specific alterations.

Apolipoprotein (apo) E is likely involved in redistributing cholesterol and phospholipids during compensatory synaptogenesis in the injured CNS. Three common isoforms of apoE exist in human (E2, E3, and E4). The apoE4 allele frequency is markedly increased in both late-onset sporadic and familial Alzheimer's disease (AD). ApoE concentration in the brain of AD subjects follows a gradient: ApoE levels decrease as a function of E2 > E3 >> E4. It has been proposed that the poor reinnervation capacity reported in AD may be caused by impairment of the apoE/low-density lipoprotein (LDL) receptor activity. To understand further the role of this particular axis in lipid homeostasis in the CNS, we have characterized binding, internalization, and degradation of human 125I-LDL to primary cultures of rat astrocytes. Specific binding was saturable, with a KD of 1.8 nM and a Bmax of 0.14 pmol/mg of proteins. Excess unlabeled human LDL or very LDL (VLDL) displaced 70% of total binding. Studies at 37 degrees C confirmed that astrocytes bind, internalize, and degrade 125I-LDL by a specific, saturable mechanism. Reconstituted apoE (E2, E3, and E4)-liposomes were labeled with 125I and incubated with primary cultures of rat astrocytes and hippocampal neurons to examine specific binding. Human LDL and VLDL displaced binding and internalization of all apoE isoforms similarly in both astrocytes and neurons. 125I-ApoE2 binding was significantly lower than that of the other 125I-apoE isoforms in both cell types. 125I-ApoE4 binding was similar to that of 125I-apoE3 in both astrocytes and neurons. On the other hand, 125I-apoE3 binding was significantly higher in neurons than in astrocytes. These isoform-specific alterations in apoE-lipoprotein pathway could explain some of the differences reported in the pathophysiology of AD subjects carrying different apoE alleles.

Animals↗
PubMed1996

Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits.

Fasting plasma total homocysteine (tHcy) concentration was measured in 380 men and 204 women selected for health on the basis of clinical history, physical examination, and normal results of a biochemical profile. We sought to define tHcy reference values in healthy individuals and to determine relations between tHcy and plasma folic acid, vitamin B-12, and pyridoxal phosphate (vitamin B-6) concentrations. Men had significantly higher plasma tHcy than women (9.7 +/- 4.9 compared with 7.6 +/- 4.1 mumol/L, x +/- SD) and lower folate concentrations (8.6 +/- 5.2 compared with 9.8 +/- 6.6 nmol/L, P < 0.05). Significant correlations were found between tHcy and uric acid, creatinine, albumin, folate, and vitamin B-12 concentrations. There was no correlation with age, body mass index, blood pressure, glucose, and total and lipoprotein lipids. When divided in quartiles of vitamin concentrations, subjects with the lowest vitamin B-12 and folate values had significantly higher tHcy concentrations than those in the other three quartiles. Interestingly, after exclusion of subjects in the lowest quartiles of folate and vitamin B-12 concentration, correlations between tHcy and vitamin concentrations were no longer observed, except for vitamin B-12 in men. Stepwise-multiple-regression analyses showed that the sex-specific influence of biological variables on tHcy concentrations was twice as important in healthy women than in healthy men. This study emphasizes the significance of sex-associated differences in the biology of homocysteine and underlines the importance of considering these in the determination of threshold values.

Adult↗
PubMed1996

Lp(a) levels and atherosclerotic vascular disease in a sample of patients with familial hypercholesterolemia sharing the same gene defect.

There is considerable variation in the severity of cardiovascular disease among patients with familial hypercholesterolemia (FH). Some reports have suggested that plasma lipoprotein(a) [Lp(a)] levels may explain such variation and that FH subjects deficient in LDL receptors, especially those with coronary heart disease, tend to have elevated Lp(a) levels. We have investigated the possible role of the LDL receptor in determining plasma Lp(a) levels in genetically homogeneous FH population and the contribution of Lp(a) to cardiovascular risk. A total of 98 FH subjects and 66 healthy first- and second-degree relatives from 30 families with FH due to the French-Canadian > 10-kilobase deletion of the LDL receptor gene were studied. A reference group of 392 normolipidemic French-Canadian participants in a Heart Health Survey was used for comparison. FH subjects were subdivided into subsets of 63 individuals free from atherosclerotic vascular disease (AVD) and 35 individuals with AVD. A complete cardiovascular evaluation was performed, and plasma lipid, lipoprotein, and Lp(a) levels were measured in all subjects in the absence of medication. Apolipoprotein (a) [apo(a)] phenotype was determined in 112 of FH and non-FH subjects. The log-transformed values for plasma Lp(a) were not significantly different among the three groups: 0.98 +/- 0.54 (mean +/- SD) in FH subjects with AVD, 0.89 +/- 0.51 in FH subjects without AVD, and 0.82 +/- 0.64 in their relatives. The distribution of the apo(a) phenotypes did not differ between the FH and non-FH groups. Comparison of two age- and sex-matched subgroups of FH subjects, with and without AVD, failed to show any differences in Lp(a) level. However, mean Lp(a) log values in the reference group (n = 392) were significantly lower than values obtained for the total FH group (0.79 +/- 0.57 versus 0.92 +/- 0.52, respectively; P < .05) but were not different from those of the unaffected family members. Thus, in our sample, the LDL receptor appears not to influence plasma Lp(a) levels; rather, these levels reflect shared apo(a) genes. The cardiovascular risk in this group of subjects with FH was related to age, male sex, total and LDL cholesterol, and higher apoB but not Lp(a) levels.

Adolescent↗
PubMed1996

Plasma concentration of apolipoprotein E in intermediate-sized remnant-like lipoproteins in normolipidemic and hyperlipidemic subjects.

Triglyceride-rich lipoprotein (TRL) remnants have been strongly implicated in the pathogenesis of atherosclerosis. To further investigate plasma remnant lipoprotein metabolism, we have determined the plasma concentration of apolipoprotein (apo) E (by polyclonal enzyme-linked immunoassay) in remnant-like lipoproteins, isolated by automated gel filtration chromatography as a fraction intermediate in size between VLDL and HDL. In normolipidemic subjects (n = 12), 1.2 +/- 0.11 mg/dL (33 +/- 2%, mean +/- SE) of total plasma apoE was associated with this fraction (termed ISL apoE). In hypercholesterolemic (type IIa, n = 12), hypertriglyceridemic (type IV, n = 12), and mixed hyperlipidemic (type IIb, n = 12) subjects, mean ISL apoE concentrations were 2.1 +/- 0.2, 2.5 +/- 0.2, and 3.8 +/- 0.4 mg/dL, respectively (P < .001 versus normal values) (45 +/- 2%, 32 +/- 2%, and 44 +/- 2% of total). ISL apoE was 8.7 +/- 1.4 mg/dL (42 +/- 3%) in type III dyslipidemic subjects (apoE2/2, n = 8). ISL apoE was positively correlated with plasma triglyceride (r = .41, P < .01), and at any given level of plasma triglyceride, subjects with an apoE2/2 or apoE3/2 phenotype tended to have a higher concentration of ISL apoE (P < .01) than apoE3/3 or E4/3 individuals. ISL apoE was also correlated (P < .001) with total plasma cholesterol (r = .66), TRL cholesterol (r = .49), TRL apoE (r = .47), LDL apoB (r = .42), and LDL+HDL triglyceride (r = .74). These results suggest that (1) a significant proportion of plasma apoE resides within an intermediate-sized remnant-like lipoprotein fraction in both normolipidemic and hyperlipidemic subjects; (2) plasma remnant lipoprotein accumulation is associated with an elevation in ISL apoE concentration; and (3) ISL apoE concentration is significantly correlated with various proatherogenic lipid parameters and may itself be a potentially important atherogenic index.

Adult↗
PubMed1996

Characterization of inherited scavenger receptor overexpression and abnormal macrophage phenotype in a normolipidemic subject with planar xanthomas.

It is proposed that, in hyperlipidemia, foam cells develop in cutaneous xanthomas from the uptake by the macrophage scavenger receptor (SR) of low density lipoproteins (LDL) that are modified due to increased residence time in plasma. We have observed extensive xanthelasmas and planar xanthomas in the absence of hyperlipidemia in two siblings. In blood monocytes from one sibling, 125I-labeled acetylated LDL (Ac-LDL) degradation and SR mRNA were 4 and 7 times higher, respectively, than in four control subjects. Among monocytes from these five individuals, variation in Ac-LDL degradation was completely accounted for by SR mRNA levels (R2 = 0.98, P < 0.001). Monocyte SR mRNA was induced upon maturation into macrophages during 7 days in culture. Mean monocyte and macrophage SR mRNA values from one sibling and six additional family members were elevated 5- and 4-fold compared to that of 16 control subjects, and elevated monocyte SR mRNA was associated with abnormally high cell-surface expression of SR epitopes. Monocytes from eight of nine family members examined displayed an unusual phenotype characterized by increased adhesion and rapid maturation into large macrophages which overaccumulated lipids. Monocyte-macrophage SR overexpression relative to control persisted even in the absence of autologous serum, consistent with a cellular abnormality. This is the first demonstration of an inherited abnormality in scavenger receptor expression and its occurrence in association with planar xanthomas.

Aged↗
PubMed1996

Apolipoprotein E polymorphism in a French Canadian population of northeastern Quebec: allele frequencies and effects on blood lipid and lipoprotein levels.

Apolipoprotein E phenotypes and plasma lipid and lipoprotein levels were determined in 435 individuals (233 men, 202 women) of French Canadian descent living in northeastern Quebec. This region is known for its high frequency of mutant genes responsible for rare genetic disorders. Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels were adjusted for age, height, weight, body mass index (BMI), and waist circumference using regressions performed separately in men and in premenopausal and postmenopausal women. The APOE allele frequencies in this population-based sample were 0.137, 0.749, and 0.114 for the *2, *3, and *4 alleles, respectively. APOE2 (APOE 2,2 and APOE 3,2) subjects had lower total and LDL cholesterol levels than APOE3 (APOE 3,3) subjects. In APOE4 (APOE 4,3 and APOE 4,4) men and postmenopausal women levels of total and LDL cholesterol and triglycerides were significantly higher than in the corresponding APOE3 subjects. The *2 allele was also found to be associated with higher triglyceride levels in men and postmenopausal women. Men of the APOE4 group also presented lower HDL cholesterol levels. Although the impact of APOE polymorphism on blood lipid and lipoprotein levels in this French Canadian population is similar to what has been reported in other white populations, the frequency of the *2 allele is among the highest ever reported. This finding is discussed in terms of the founder effect characterizing the Quebec population.

Abnormalities, Multiple↗
PubMed1996

Lack of association of the apolipoprotein A-I-C-III-A-IV gene XmnI and SstI polymorphisms and of the lipoprotein lipase gene mutations in familial combined hyperlipoproteinemia in French Canadian subjects.

Familial combined hyperlipoproteinemia (FCH) is a common familial lipoprotein disorder characterized by elevated plasma cholesterol and triglyceride levels with segregation in first-degree relatives. Most affected subjects with FCH have elevated plasma levels of apolipoprotein (apo) B. The disorder results from oversecretion of hepatic apoB-containing lipoprotein particles. The genetic defect(s) are unknown. Previous work has suggested that genetic polymorphisms of the apoA-I gene and functional abnormalities of the lipoprotein lipase (LPL) gene are associated with FCH. We investigated the XmnI and SstI restriction fragment length polymorphisms (RFLP) of the apoA-I gene in FCH subjects of French Canadian descent. We also investigated three common functional mutations of the lipoprotein lipase (LPL) gene (LPLGly188Glu, LPLPro207Leu, and LPLAsp250Asn) in French Canadians that account for approximately 97% of cases of complete LPL deficiency in the province of Québec, Canada. We identified and characterized 54 FCH probands in lipid clinics and examined at least one first-degree relative. There were 37 men and 17 women (mean age 48 +/- 9 and 58 +/- 8 years, respectively). None of the probands had diabetes mellitus; mean plasma glucose was 5.5 mmol/L. High blood pressure was diagnosed in 32% of men and 29% of women. The body mass index (weight (kg)/height(m2)) was elevated in probands (27 +/- 4 for men and 26 +/- 4 for women). Mean plasma levels of cholesterol (C) was 7.6 +/- 1.5 mmol/L, triglycerides 3.5 +/- 1.6 mmol/L, LDL-C 4.9 +/- 1.2 mmol/L, HDL-C 1.0 +/- 0.3 mmol/L, and apoB 1.83 +/- 0.67 g/L in the probands. Allele frequency of the rare alleles of the XmnI and SstI RFLP was not significantly different from a healthy reference group. In several families studied, the XmnI and SstI RFLP did not unequivocally segregate with the FCH phenotype. There was no significant effect of the presence or absence of the XmnI or SstI RFLP's on plasma lipids, lipoprotein cholesterol or apoB levels. Only one FCH proband was found to have a mutation of the LPL gene (Gly188Glu), and this did not segregate with the FCH phenotype in the family. We conclude that in our highly selected group of FCH subjects of French Canadian descent, the XmnI and SstI RFLPs of the apoA-I gene and common functional mutations of the LPL gene resulting in complete LPL deficiency are not associated with FCH.

Adult↗
PubMed1996

A lipid clinic associated with a research laboratory working on dyslipoproteinemias and atherosclerosis.

BACKGROUND: Atherosclerosis is a widespread disease in affluent societies. Dyslipidemias and susceptibility genes enhance the likelihood of developing coronary artery disease, its most dreaded complication. There is a need for rapid transfer of advances in knowledge to the care of patients with conditions predisposing to atherosclerosis. A lipid clinic associated with a research laboratory, a 'lipid unit', provides an optimal setting to achieve this goal. OBJECTIVE: To describe the organization, function, usefulness and modus operandi of a lipid unit. DESIGN: Review of nearly 30 years' experience in directing a lipid unit. SETTING: A basic research laboratory associated with an outpatient lipid clinic and day care unit in a clinical research institute with academic affiliations. MEASUREMENTS: Examples of advances made within the framework of a lipid unit are used for illustration. RESULTS: Major advantages may be derived from a close interaction between clinical and laboratory staffs in a lipid unit and the medical community at large. Such interactions provide a strong incentive for research, foster discoveries of new diseases and facilitate transfer of new knowledge in diagnosis and treatment to patient care. A referral centre for complex problems allows access to unusual cases which may become a starting point for research and discovery. An integrated lipid unit may become a major contributor to medical education and community health care when a dialogue is established with referring physicians. CONCLUSIONS: The concept of an integrated lipid unit with a role in medical education and health care is viable.

Ambulatory Care Facilities↗
PubMed1995

Occurrence and biological effects of cholesteryl sulfate on blood platelets.

Although the exact function of cholesteryl sulfate (CS) is unknown, it is present in low concentration in lipoproteins, in red blood cells and spermatozoa. In the present study, we investigated whether CS is present in blood platelets and its possible biological involvement in platelet function. Extensively washed platelets were prepared from rat and human blood. After lipid extraction and thin layer chromatography (TLC) on silica gel, a compound with the same mobility as authentic CS was isolated and identified by two different methods: (1) without hydrolysis, negative ion fast atom bombardment combined with tandem mass spectrometry (MS/MS); (2) after acidic hydrolysis, identification of cholesterol (Chol) by TLC and gas chromatography-MS. CS concentrations measured using beta-sitosteryl sulfate as internal standard in normal rat or human platelets were in the range of 164-512 pmol/10(9) platelets. This represented less than 1% of cell Chol. Biological effects of CS on platelet function were studied in vitro. CS incubated with rat platelets either as methanol solution or as albumin-bound complex potentiated the ADP- or thrombin-induced aggregation and serotonin secretion. The results of platelet sterol analysis indicated that CS was incorporated into platelet membrane and did not significantly change the platelet cholesterol composition. The potentiating effect of CS on platelet-induced aggregation and secretion was not obtained with cholesterol, cholesteryl acetate or estrone. In contrast, an inhibitory effect of estrone sulfate was observed. These results indicate that both the sulfate group and the cholesterol moiety are involved in the pro-aggregant property of CS. In addition, platelet mediators seem to be implicated in the mechanism since the thrombin-induced production of thromboxane B2, the stable end-product of arachidonic acid metabolism, was also enhanced in the presence of CS. These results suggest a new role for CS which may be involved in the modulation of platelet function.

Animals↗
PubMed1995

Unexpected consequences of deletion of the first two repeats of the ligand-binding domain from the low density lipoprotein receptor. Evidence from a human mutation.

Heterozygosity for a 5-kilobase (kb) deletion of the first two ligand-binding repeats (exons 2 and 3) of the low density lipoprotein (LDL) receptor (R) gene (LDL-R delta 5kb) confers familial hypercholesterolemia (FH). The FH phenotype is unexpected based on previous site-directed mutagenesis showing that deletion of exons 2 and 3 resulted in little or no defect in LDL-R activity. In the present study, we took unique advantage of the ability to distinguish the LDL-R delta 5kb from the normal receptor on the basis of size, in order to resolve this apparent discrepancy. Fibroblasts from heterozygotes for the LDL-R delta 5kb displayed 50% of normal capacity to bind LDL and beta-VLDL, apparently due to lower receptor number. Cellular mRNA for the delta 5kb allele was at least as abundant as that for the normal allele. Immunoblotting and cell binding assays with anti-LDL-R antibody IgG-4A4 demonstrated normal synthesis and transport of the delta 5kb receptor. Ligand blotting demonstrated that the delta 5kb receptor displayed minimal or no ability to bind LDL or beta-VLDL. Thus, in contrast to transfected cell lines, in human fibroblasts, the first two cysteine rich repeats of the LDL-R appear functionally necessary. These characteristics of the LDL-R delta 5kb in human fibroblasts explain the in vivo phenotype of carriers.

Base Sequence↗
PubMed1995

Impact of apolipoprotein E genotype variation on means, variances, and correlations of plasma lipid, lipoprotein, and apolipoprotein traits in octogenarians.

The impact of apolipoprotein (apo) E genotype variation on means, variances and correlations between plasma lipid traits was studied in male and female octogenarians. Females had significantly higher mean levels of all 10 of the measured plasma lipid traits than males. The subset of concomitants (i.e., age, height, weight, body mass index, glucose and uric acid) that made a statistically significant contribution to interindividual variability was different in males and females for every trait considered. Gender-specific associations between variation in apo E genotype and variation in particular measures of lipid metabolism, adjusted for concomitant variation, were observed: in females there were no statistically significant associations while in males the means of the three common apo E genotypes were significantly different for adjusted measures of total cholesterol, low density lipoprotein cholesterol and low density lipoprotein-apo B. The common apo E genotypes were heterogeneous with respect to intragenotypic variance for adjusted log-transformed triglyceride levels in females only. Finally, the three common apo E genotypes were heterogeneous with respect to the correlation between traits, adjusted for concomitant variation, and gender influenced the manner in which the genotypes differed for specific correlations. This study documents that variation in the apo E gene has a significant impact on means, variances and correlations of plasma lipid traits in octogenarians, but the effects are context-, that is gender- and age-, dependent.

Aged↗
PubMed1995

Coronary artery disease in heterozygous familial hypercholesterolemia patients with the same LDL receptor gene mutation.

BACKGROUND: Familial hypercholesterolemia (FH), an autosomal codominant disease, is characterized by high levels of LDL cholesterol and a high incidence of coronary artery disease (CAD). To date, genetic heterogeneity has hindered the proper assessment of the relation between risk factors and CAD in FH patients. METHODS AND RESULTS: We studied the association between CAD and common risk factors in a sample of 263 French Canadian FH patients (147 women, 116 men) carrying the same > 10-kb deletion of the LDL receptor gene. Thirty-five women and 54 men had CAD. The mean age of onset of CAD was 45.6 +/- 12.7 years in women and 38.8 +/- 9.4 years in men. Multiple logistic regression analyses were performed to test the association between CAD and age, tendon xanthomas, cigarette smoking, hypertension, diabetes mellitus, apolipoprotein E polymorphism, total plasma cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, and lipoprotein(a) [Lp(a)]. In FH women, significant multivariate predictors were age (odds ratio, 1.10 for 1 year; P < .0001), VLDL cholesterol (odds ratio, 3.85 for 1 natural log unit; P < .002), and LDL cholesterol (odds ratio, 1.42 for 1 mmol/L; P < .02). In FH men, age (odds ratio, 1.08 for 1 year; P < .0001) and HDL cholesterol (odds ratio, 0.14 for 1 mmol/L; P = .05) were significant predictors of disease. Lp(a) was not a significant predictor in univariate or multivariate analyses. CONCLUSIONS: This study suggests that increased risk of CAD in FH is not solely due to elevated LDL cholesterol levels and demonstrates a sex-specific lipoprotein influence on CAD in a large sample of FH patients carrying the same LDL receptor gene defect.

Adult↗
PubMed1995

Molecular analysis of human prorenin prosegment variants in vitro and in vivo.

The aspartyl protease renin, an important modulator of blood pressure in humans, is present in the circulation not only in its active form, but also as an inactive precursor, prorenin, in which a 43-amino acid prosegment blocks access of the substrate to the active site of the enzyme. Site-directed mutagenesis of the prosegment has led to the following conclusions. 1) Maintenance of the enzymatically inactive state of prorenin requires a short peptide sequence between positions 10P and 20P (where P denotes prosegment and numbering is relative to amino terminus) of the prosegment; and 2) there is an inverse relationship between the ability of prosegment mutations to activate and their effect on the secretion of the various prorenins, suggesting that this same region of the prosegment plays a critical role in the biosynthesis of human prorenin. Since these results demonstrated that single amino acid mutations could activate human prorenin to varying degrees, mutations in this region of the renin gene could be clinically important in humans. To test this hypothesis, genomic screening was carried out on the corresponding region of the human renin gene (exon 2) in a cohort of patients selected for a likely familial component to their hypertension. While this study identified a novel polymorphism in exon 2 of the human renin gene, evidence was not obtained for either the presence of prosegment mutations or the association of the novel polymorphism with hypertension in the patient population studied. In conclusion, both structure-function studies and genetic screening suggest that mutation of the prorenin prosegment is an unlikely factor in activation of the renin-angiotensin system in humans.

Amino Acid Sequence↗
PubMed1995

Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate.

We determined plasma levels of homocysteine in 584 healthy subjects (380 men and 204 women) from a major utility company in the province of Québec, Canada, and in 150 subjects (123 men and 27 women) with angiographically documented coronary artery disease (CAD) (age < 60 years). Plasma levels of vitamins B12, B6, pyridoxal phosphate (a vitamin B6 derivative), and folate were also determined. Mean homocysteine levels were higher (p < 0.05) in the bottom quartiles for folate, vitamin B12, and pyridoxal phosphate. A significant correlation was noted between homocysteine levels and folate and vitamin B12 levels. No significant correlation was found between plasma homocysteine levels and age, lipids and lipoprotein cholesterol, glucose, and the presence of hypertension or cigarette smoking in healthy subjects or in patients with CAD. Control men had higher homocysteine levels than control women (p < 0.005). Men and women with CAD had higher levels of homocysteine than controls (11.7 +/- 5.8 vs 9.7 +/- 4.9 nmol/ml [p < 0.001] and 12.0 +/- 6.3 vs 7.6 +/- 4.1 nmol/ml, p < 0.01, respectively). Women and men with CAD had similar homocysteine levels. The proportion of patients with CAD having homocysteine levels > 90th percentile of controls was 18.1% for men and 44.4% for women (both p < 0.01). Significantly lower pyridoxal phosphate levels were seen in subjects with CAD, men and women combined (27.7 +/- 29.5 vs 42.1 +/- 38.4 ng/ml, p < 0.005). No significant differences were observed for B12, folate, or total B6.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Enhanced susceptibility of cholesteryl sulfate-enriched low density lipoproteins to copper-mediated oxidation.

Cholesteryl sulfate (CS) is a minor component of cell membranes, also present in lipoproteins, and its exact function is unknown. Since oxidation of low density lipoproteins (LDL) is thought to be an important determinant of atherogenesis, we investigated the influence of CS enrichment on copper-mediated oxidation of LDL. CS was found to act as a pro-oxidant, as measured by lipid oxidation parameters. The results also suggest that these effects were dependent on the sulfate group since pure cholesterol or cholesteryl acetate did not promote Cu(2+)-mediated oxidation. Our findings imply that CS may affect the oxidizability and hence the potential atherogenicity of LDL.

Arteriosclerosis↗
PubMed1995

Pro-oxidant effects of 7-hydroperoxycholest-5-en-3 beta-ol on the copper-initiated oxidation of low density lipoprotein.

In low density lipoproteins (LDL) supplemented with aged cholesterol and oxidized in the presence of Cu2+, an increase of the lipid oxidation parameters was observed compared with pure cholesterol-enriched LDL. A compound, identified as 7-hydroperoxycholesterol (7HPC), isolated from aged cholesterol and added to LDL, reproduced the above effects. The results indicate that the pro-oxidant effect of 7HPC is dependent on the hydroperoxy group since the corresponding alcohol derivative, 7 alpha-hydroxycholesterol, had no such effect. These data suggest that among the LDL-associated lipid peroxides, cholesterol peroxides may have important implications in the susceptibility of this lipoprotein to oxidation.

Cholesterol↗