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G Bittolo-Bon

Publications and source records attributed to G Bittolo-Bon.

18 recordsLinked to original sources
PubMed2003

Hypertriglyceridemia is associated with increased insulin resistance in subjects with normal glucose tolerance: evaluation in a large cohort of subjects assessed with the 1999 World Health Organization criteria for the classification of diabetes.

The current study retrospectively examined the association between insulin resistance and plasma triglycerides (TG) in a group of subjects with normal glucose tolerance. Among 1,434 subjects consecutively undergoing a standard oral glucose tolerance test (OGTT) between 1993 and 1998, 567 (age, 15 to 78 years) were classified as having a normal glucose tolerance according to the 1999 World Health Organization (WHO) criteria and were selected for the study. Serum insulin was measured by radioimmunoassay (INSI-CTK, Dia Sorin, Saluggia, Italy). Intra-assay and interassay coefficients of variation for the method were less than 4% and less than 8.5%, respectively. Insulin resistance was calculated by a homeostasis model assessment (HOMA(IR) = fasting serum insulin [mU/mL] x fasting blood glucose [mmol/L]/22.5). A very significant correlation was found between HOMA(IR) and plasma TG (r = 0.27, P < 1.02E(-10)). Multiple regression analyses confirmed plasma TG as independent variables explicative of HOMA(IR). When subjects were evaluated according to tertiles of TG, those in the upper two tertiles were older (P <.001) and presented higher body mass index (BMI) values (P <.0001) in comparison to subjects in the lower tertile. A positive trend (analysis of variance [ANOVA]) was found in regard to systolic (P <.05) and diastolic blood pressure (P <.0001), fasting blood glucose (P <.01), fasting serum insulin (P <.0001), and total cholesterol (P <.0001), while a negative trend was found in regard to high-density lipoprotein cholesterol (HDL-C) (P <.0001). Insulin resistance, calculated as HOMA(IR), was higher in the upper two tertiles of TG in comparison to the lower tertile (P <.001 and P <.0001, respectively), with a statistically significant trend for the entire group (first tertile, 1.85 +/- 0.94; second tertile, 2.28 +/- 1.10; third tertile, 2.65 +/- 1.71; ANOVA: P <.0001). In conclusion, this study shows an association between high levels of circulating TG and insulin resistance in patients with normal glucose tolerance seen in an atherosclerosis prevention clinic. This association is also present at levels of plasma TG considered to be normal and is associated with a cluster of cardiovascular risk factors.

Adult↗
PubMed2001

Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL(-).

A subpopulation of low-density lipoproteins (LDL) is present in human plasma that contains lipid hydroperoxides and is more negatively charged (LDL(-)) than normal native LDL. By circular dichroism and tryptophan lifetime measurements we found that apoB-100 secondary structure is markedly decreased and its conformation is severely altered in LDL(-). The low tryptophan fluorescence intensity confirms the oxidative degradation of the lipoprotein, and the very long lifetime value of one of its decay components indicates a low polarity environment for the remaining unbleached residues. Either a peculiar folding or, most likely, a sinking of the apoB-100 into the lipid core can account for the observed long lifetime component. Oxidation in vitro produces a similar unfolding of the apolipoprotein but the lifetime of tryptophan fluorescence is shifted to lower values, indicating that the denatured apoprotein remains at the hydrophilic surface of the lipoprotein particle. A disordering and an increased polarity of the LDL(-) surface lipids was demonstrated by measuring the generalized polarization of 2-dimethylamino-6-lauroylnaphthalene (Laurdan). The looser monolayer packing apparently favors the new conformation of apoB-100 and its sinking into a more hydrophobic environment, possibly accounting for it reduced receptor binding properties.

2-Naphthylamine↗
PubMed1999

Analytical capillary isotachophoresis of total plasma lipoproteins: a new tool to identify atherogenic low density lipoproteins.

Plasma low density lipoproteins from 20 patients were separated by capillary isotachophoresis (ITP). In each patient the apparent diameter of the predominant LDL peak on whole plasma was also determined by nondenaturing gradient gel electrophoresis. Furthermore the concentration of the more electronegatively charged in vivo oxidized LDL- was accomplished using anion exchange high pressure liquid chromatography. By analytical capillary ITP of whole plasma lipoproteins, prestained with a lipophilic dye, LDL were separated into four subfractions. Usually, the predominant subfraction was the slow migrating LDL4, followed by LDL3, and then by the faster LDL2 and LDL1. Slow migrating LDL4 correlated negatively with plasma triglycerides and LDL- and positively with plasma high density lipoprotein (HDL) cholesterol and with the LDL diameter, while the faster LDL1 showed an inverse behavior. The LDL1 + LDL2 to LDL3 + LDL4 ratio showed a strong positive correlation with LDL- concentration (r = 0.87; P < 0.001) and a highly significant inverse correlation with the LDL particle diameter (r = -0.74; P < 0.001). At least three highly atherogenic LDL that could be found in human plasma, namely oxidized, glycated and small-dense, are characterized by a greater electric charge. The LDL profile from capillary ITP and the relative prevalence of faster or slower migrating LDL fractions could indicate the presence of more atherogenic LDL.

Adult↗
PubMed1998

Effect of thyroid function on LDL oxidation.

In this study, the effect of different levels of thyroid hormone and metabolic activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16 patients with hyperthyroidism, 16 with hypothyroidism, and 16 age- and sex-matched healthy normolipidemic control subjects, the native LDL content in lipid peroxides, vitamin E, beta-carotene, and lycopene, as well as the susceptibility of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism was associated with significantly higher lipid peroxidation, as characterized by a higher native LDL content in lipid peroxides, a lower lag phase, and a higher oxidation rate than in the other two groups. This elevated lipid peroxidation was associated with a lower LDL antioxidant concentration. Interestingly, hypothyroid patients showed an intermediate behavior. In fact, in hypothyroidism, LDL oxidation was significantly lower than in hyperthyroidism but higher than in the control group. Hypothyroidism was also characterized by the highest beta-carotene LDL content, whereas vitamin E was significantly lower than in control subjects. In hyperthyroidism but not in the other two groups, LDL oxidation was strongly influenced by free thyroxine blood content. In fact in this group, the native LDL lipid peroxide content and the lag phase were directly and indirectly, respectively, related to free thyroxine blood levels. On the contrary, in hypothyroidism LDL oxidation was strongly and significantly related to serum lipids. In conclusion, both hypothyroidism and hyperthyroidism are characterized by higher levels of LDL oxidation when compared with normolipidemic control subjects. In hyperthyroid patients, the increased lipid peroxidation was strictly related to free thyroxine levels, whereas in hypothyroidism it was strongly influenced by serum lipids.

Antioxidants↗
PubMed1997

LDL- is a lipid hydroperoxide-enriched circulating lipoprotein.

A subclass of LDL described on the basis of its greater electronegativity and oxidative status is further characterized using a new, highly sensitive single photon counting technique to measure lipid hydroperoxides. We describe in this report that these particles, which we refer to as LDL-, are enriched in lipid peroxides and other peroxidation products as compared to the bulk of the unmodified, normal LDL (nLDL) recovered from human plasma. This chemiluminescence-based, single photon counting technique has unique advantages in that analyses are performed on whole LDL, thus avoiding artifactual lipid peroxidation during lipid extraction. Evidence for increased amounts of lipid hydroperoxides in LDL- versus nLDL are in agreement with other analytical methods such as measurement of conjugated dienes as well as cholesterol oxidation products. LDL- also has lower proportions of polyunsaturated fatty acids than nLDL. Analysis of the amino acid composition of apoB-100 and fatty acid composition of total LDL lipids also revealed major differences between nLDL and LDL- consistent with an oxidative modification of the latter. Thus, LDL- has significantly lower proportions of the oxidizable amino acids histidine and lysine, and marked differences in other neutral and acidic amino acids. The deficit in specific amino acids is in agreement with a reduced TNBS reactivity and increased relative electrophoretic mobility of LDL-. We postulate that LDL- is a major carrier of lipid hydroperoxides associated with plasma LDL and may arise from oxidative events in the vasculature and/ or by ingestion of peroxide-enriched meals.

Amino Acids↗
PubMed1996

Blood pressure, serum lipids, and fatty acids in populations on a lake-fish diet or on a vegetarian diet in Tanzania.

Major risk factors for coronary heart disease were assessed in two populations of Tanzania, one on a fish diet (FD) living along the coast of Lake Nyasa, and the other, mainly on a vegetarian diet (VD), living in a farming area. Lower blood pressure values were found in the FD subjects (n = 618) vs. VD (n = 618) (systolic blood pressure, SBP, 120 +/- 15 vs. 135 +/- 20, P < 0.01; diastolic blood pressure, DBP, 70 +/- 9 vs. 78 +/- 11, P < 0.01, respectively). In an FD subgroup (n = 61), total cholesterol (TC) (122 vs. 136 mg/dL, P < 0.01); triglycerides (TG) (82 vs. 105 mg/dL, P < 0.01); and lipoprotein (a) [Lp(a)] (19.9 +/- 18.4 vs. 32.3 +/- 22.4, P < 0.001) were lower than in a VD subgroup (n = 55). Serum fatty acids (FA) in the FD subgroup were as follows: eicosapentaenoic acid (EPA) (20:5) 2.48 vs. 0.72%, docosahexaenoic acid (DHA) (22:6) 5.93 vs. 1.49%, vs. the VD, respectively. Arachidonic acid (AA) (20:4n-6) also was higher in the FD vs. the VD group (9.85 vs. 8.30%, P < 0.05), whereas 18:2n-6 was about double (23.97 and 14.85%) in VD vs. FD. The peculiar serum FA pattern in FD reflected the FA of dietary fish. In fact, in four main species of lake fish, DHA was 8-19%, higher than EPA (1.8-4.2%), in contrast with the situation in cold-water fish, and AA was 5.8-8%, higher than in cold-water fish. The data, obtained in populations strictly on natural, unprocessed, low-fat diets, show that a diet based on freshwater fish results in lower BP, serum TC, TG, and Lp(a), and suggests that serum AA is not reduced when the major dietary n-3 is DNA rather than EPA.

Animals↗
PubMed1996

Contribution of an in vivo oxidized LDL to LDL oxidation and its association with dense LDL subpopulations.

Oxidative modification of LDL is thought to be a radical-mediated process involving lipid peroxides. The small dense LDL subpopulations are particularly susceptible to oxidation, and individuals with high proportions of dense LDL are at a greater risk for atherosclerosis. An oxidatively modified plasma LDL, referred to as LDL-, is found largely among the dense LDL fractions. LDL- and dense LDL particles also contain much greater amounts of lipid peroxides compared with total LDL or the more buoyant LDL fractions. The content of LDL- in dense LDL particles appears to be related to copper- or heme-induced oxidative susceptibility, which may be attributable to peroxide levels. The rate of lipid peroxidation during the antioxidant-protected phase (lag period) and the length of the antioxidant-protected phase (lag time) are correlated with the LDL- content of total LDL. Once LDL oxidation enters the propagation phase, there is no relationship to the initial LDL- content or total LDL lipid peroxide or vitamin E levels. Beyond a threshold LDL- content of approximately 2%, there is a significant increase in the oxidative susceptibility of nLDL particles (ie, purified LDL that is free of LDL-), and this susceptibility becomes more pronounced as the LDL- content increases. nLDL is resistant to copper- or heme-induced oxidation. The oxidative susceptibility is not influenced by vitamin E content in LDL but is strongly inhibited by ascorbic acid in the medium. Involvement of LDL(-)-associated peroxides during the stimulated oxidation of LDL is suggested by the inhibition of nLDL oxidation when LDL- is treated with ebselen prior to its addition to nLDL. Populations of LDL enriched with LDL- appear to contain peroxides at levels approaching the threshold required for progressive radical propagation reactions. We postulate that elevated LDL- may constitute a pro-oxidant state that facilitates oxidative reactions in vascular components.

Adult↗
PubMed1995

Naturally occurring modified low density lipoproteins are similar if not identical: more electronegative and desialylated lipoprotein subfractions.

Previous studies demonstrated that more electronegative low density lipoprotein (LDL) isolated from human blood by ion exchange chromatography has a chemical composition and physical properties similar to desialylated LDL obtained by lectin chromatography (Avogaro et al., 1988; Orekhov et al., 1989). In this study, sialic acid content and percentage of desialylated LDL in the electronegative LDL (LDL-) subfraction have been investigated. The sialic acid content of the LDL- was 2- to 6-fold lower than that of native LDL and close to that of desialylated LDL. In the native LDL subfraction, 83% of lipoprotein particles did not bind to the Ricinus communis agglutinin, indicating lack of terminal galactose, presumably appearing as a result of desialylation of LDL carbohydrate chains. By contrast, a major proportion of human LDL- (81%) was bound to the lectin. It was also found that the desialylated LDL subfraction consists of 88% LDL-. Native LDL did not affect the contents of free and esterified cholesterol in intimal cells cultured from grossly normal human aorta, while LDL- and desialylated LDL induced a 1.5- to 3-fold increase in the intracellular content of cholesteryl esters. Thus, LDL- is desialylated LDL which induces lipid accumulation in intimal cells. Our findings suggest that the LDL- particle is similar if not identical to the desialylated LDL particle.

Adult↗
PubMed1994

Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

Using ion exchange high pressure liquid chromatography, total plasma low density lipoprotein (LDL) from 30 hypercholesterolemic and 10 normocholesterolemic cynomolgus monkeys was subfractionated into unmodified LDL (n-LDL) and more negatively charged LDL (LDL-). In hypercholesterolemic monkeys, the absolute LDL-cholesterol level was 16.54 +/- 2.82 mg/dl (mean +/- SE) whereas in normocholesterolemic monkeys it was 2.39 +/- 0.12 mg/dl (P < 0.0001); the percentage of LDL- was 5.2 +/- 0.71% and 4.9 +/- 0.19% of the total LDL for hypercholesterolemic versus normocholesterolemic monkeys, respectively. LDL- averaged 5% and n-LDL 95% of the total plasma LDL cholesterol. To confirm and further elucidate the oxidative nature of LDL-, cholesterol and cholesterol oxide contents of LDL- and n-LDL were determined by capillary gas chromatography; 53.98 +/- 2.24% (mean +/- SE) of the LDL- cholesterol was oxidized whereas in n-LDL only 10.70 +/- 1.06% of the cholesterol was oxidized (P < 0.00001). The spectrum of oxysterols identified, which was similar for LDL- and n-LDL, suggested a free radical-mediated process for cholesterol oxidation. The principal oxysterols identified were: cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-diene-7-one, cholest-5-ene-3 beta, 7 beta-diol, 5,6 beta-epoxy-5 beta-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 beta-ol, 5 alpha-cholestan-3 beta,5,6 beta-triol, 3 beta-hydroxycholest-5-ene-7-one, and cholest-5-ene-3 beta,25-diol. To model one of the steps in the possible mechanism of atherogenesis, the cytotoxicity of LDL- was demonstrated to be greater against subconfluent than confluent aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Some questions concerning a small, more electronegative LDL circulating in human plasma.

Atherosclerosis and its complications are prevalent worldwide with a high prevalence in western societies. The disease may sometimes be explained by a defect of low density lipoprotein (LDL) specific receptors. However, the prevalence of receptor defect is rather rare and a large body of evidence supports the possibility that an alternative pathway, the so-called "scavenger pathway", constitutes the gate through which cholesterol enters into the parietal wall and gives origin to the "foam cell". Experimental work has clearly demonstrated that LDL may be modified under the action of chemical and biological offenders, all of which make the LDL an "alien". Some papers suggest that the modifications of LDL may occur also "in vivo" in the microenvironment of the vascular vall. In 1988 we were able to record two LDL subfractions in human plasma; the more electronegative minor subfraction shares many of the peculiar traits of LDLs modified "in vitro". The present article stresses all the points which support the hypothesis that the small more electronegative LDL circulating modified LDL, may represent a certain amount of possibly oxidative in origin.

Animals↗
PubMed1991

Characterization of a more electronegatively charged LDL subfraction by ion exchange HPLC.

Low density lipoproteins (LDL), collected from 32 normal male subjects (aged 30-60), were subfractionated by high resolution ion exchange chromatography (IE-HPLC). By this procedure two LDL subfractions were eluted. The first corresponds to normal LDL (nLDL); while the second one corresponds to a more electronegative subfraction, called LDL-. The mean percentage contribution of LDL- to native plasma LDL was of 3.9% (range 0.5-9.8%). The percentage concentration of LDL- in total native LDL did not correlate with plasma total cholesterol, triglycerides, and LDL cholesterol, whereas a significant negative correlation with high density lipoprotein cholesterol was found (r = -.38; p less than .05). LDL- was negatively correlated with LDL phospholipids (r = -.59; p less than .001), and with the LDL vitamin E content (r = -.63; p less than .001), and positively correlated with LDL proteins (r = -.35; p less than .05) and the content of thiobarbituric acid reactive substances (TBARS) in total LDL (r = .43; p less than .05). The TBARS molar content of LDL- was three times higher than in nLDL, with a mean concentration in LDL- of 7.3 mol/mol lipoprotein. By preparative IE-HPLC significant differences of the LDL- chemical composition were observed. The percentage content of cholesterol esters and of phospholipids was decreased, whereas proteins and free cholesterol were increased. Analysis by sodium dodecyl sulphate polyacrylamide gel electrophoresis revealed that besides apolipoprotein B-100 there was evidence of peptides with a higher molecular weight in LDL-.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Probucol protects low-density lipoproteins from in vitro and in vivo oxidation.

Twelve patients with primary hypercholesterolemia were treated for 12 weeks with probucol (500 mg b.i.d.). For each patient low density lipoproteins (LDL), isolated by ultracentrifugation were subfractionated by ion exchange high resolution chromatography in order to evaluate the content of a more electronegatively charged LDL (LDL-), a small subfraction that probably represent a circulating oxidatively modified lipoprotein. The treatment induced a 17% reduction of total LDL and 43% reduction of LDL-. By thin layer chromatography the probucol content in LDL- was a quarter of that in normally charged LDL. Under basal conditions, native LDL incubated for 24 h with 3 microM copper sulphate shows a net increase in electrophoretic mobility, an increase in relative fluorescence intensity and a reduction in vitamin E content, thus indicating peroxidative damage. After treatment with probucol, no significant changes of electrophoretic mobility, fluorescence and vitamin E content are detectable. LDL isolated from patients treated with probucol thus become resistant to oxidation by copper ions. The observed reduction of LDL- after treatment with probucol, confirms in vivo the antioxidant role of the drug and support the hypothesis that circulating LDL- may be linked to an oxidative process occurring in vivo.

Adult↗