Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects.

Graaf, Jacqueline de; Hak-Lemmers, H.L.M.; Hectors, M. P. C.; Demacker, P.N.M.; Hendriks, Jan C.M.; Stalenhoef, Anton F. H.

doi:10.1161/01.atv.11.2.298

Cited by 660 publications

(274 citation statements)

References 51 publications

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“…The vitamin E concentrations in LDL were deter mined by high performance liquid chromatography (HPLC) as described previously [27]. LDL fatty acid composition was measured as described previously [27], and was expressed as a percentage of total fatty n /i 1 7 4 …”

Section: Other Methodsmentioning

confidence: 99%

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Lipid peroxidation and susceptibility of low‐density lipoprotein to in vitro oxidation in hyperhomocysteinaemia

Blom

Kleinveld

Boers

et al. 1995

Eur J Clin Investigation

103

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Abstract. The pathobiochemical mechanism of arte riosclerosis in hyperhomocysteinaemiu has not yet been elucidated. In vitro studies have shown that the cytotoxic properties o f homocysteine can be ascribed to its generation of reactive oxygen species, We studied lipid peroxidation, both in vivo and in vitro, in 10 homozygous cystathionine synthase-deficicnt (GSD) patients and in a control group of 10 healthy subjects of comparable age and sex. The susceptibility of low-density lipoprotein (LDL) from hyperhomocysteinaemic patients to oxidation was determined in vitro by continuously measuring the conjugated diene production induced by incubation with copper ions, Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent o f oxidation (expressed as total diene production) of LDL from CSD patients were not significantly different from those o f LDL from controls. Furthermore, the time needed to reach maximal diene production, i.e. t(max), was similar lor LDL from patients and controls. In addition, the vitamin E concentrations in LDL o f CSD patients and controls were similar. The mean concentration (d::SD) o f plasma thiobarbituric acid reactive sub stances (TBARS), an indicator of in vivo lipid per oxidation, was 2-2 ± 0*7 //mol L 1 in CSD patients, a lower value than that measured in the matched con trols (5*0 ± 2*0 /¿mol L 1). investigation o f in vivo and in vitro parameters o f lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomo cysteinaemia is unlikely to be due to increased lipid peroxidation.Keywords. Atherosclerosis, cystathionine synthase deficiency, hyperhomocysteinaemia, lipid peroxi dation, low-density lipoprotein. Abbreviations* CSD, cystathionine /2-synthase defi ciency; LDL, low-density lipoprotein; TBARS, thio barbituric acid reactive substances.

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Section: Other Methodsmentioning

confidence: 99%

“…LDL fatty acid composition was measured as described previously [27], and was expressed as a percentage of total fatty n /i …”

Section: Other Methodsmentioning

confidence: 99%

Lipid peroxidation and susceptibility of low‐density lipoprotein to in vitro oxidation in hyperhomocysteinaemia

Blom

Kleinveld

Boers

et al. 1995

Eur J Clin Investigation

103

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“…The retained LDL particles in the intima are exposed to modification under conditions of oxidative stress. Small dense LDL shows an increased susceptibility to oxidation and glycation of LDL further aggravating this susceptibility to oxidation [132,133,134,135]. A debated question is whether the size of LDL or its integral physical properties determine LDL oxidisability.…”

Section: Why Is Small Dense Ldl Highly Atherogenic?mentioning

confidence: 99%

Diabetic dyslipidaemia: from basic research to clinical practice*

2003

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The recognition that the increase of plasma triglyceride rich lipoproteins (TRLs) is associated with multiple alterations of other lipoproteins species that are potentially atherogenic has expanded the picture of diabetic dyslipidaemia. The discovery of heterogeneity within major lipoprotein classes VLDL, LDL and HDL opened new avenues to reveal the specific pertubations of diabetic dyslipidaemia. The increase of large VLDL 1 particles in Type 2 diabetes initiates a sequence of events that generates atherogenic remnants, small dense LDL and small dense HDL particles. Together these components comprise the atherogenic lipid triad. Notably the malignant nature of diabetic dyslipidaemia is not completely shown by the lipid measures used in clinical practice. The key question is what are the mechanisms behind the increase of VLDL 1 particles in diabetic dyslipidaemia? Despite the advances of recent years, our understanding of VLDL assembly and secretion is still surprisingly incomplete. To date it is still unclear how the liver is able to regulate the amount of triglycerides incorporated into VLDL particles to produce either VLDL 1 or VLDL 2 particles. The current evidence suggests that the machinery driving VLDL assembly in the liver includes (i) low insulin signalling via PI-3 kinase pathway that enhances lipid accumulation into "nascent" VLDL particles (ii) up-regulation of SREBP-1C that stimulates de novo lipogenesis and (iii) excess availability of "polar molecules" in hepatocytes that stabilizes apo B 100. Recent data suggest that all these steps could be fundamentally altered in Type 2 diabetes explaining the overproduction of VLDL apo B as well as the ability of insulin to suppress VLDL 1 apo B production in Type 2 diabetes.Recent discoveries have established the transcription factors including PPARs, SREBP-1 and LXRs as the key regulators of lipid assembly in the liver. These observations suggest these factors as a new target to tailor more efficient drugs to treat diabetic dyslipidaemia. [Diabetologia (2003) 46:733-749]

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“…[46][47][48] Small, dense LDL subfractions are more susceptible to oxidative modification and therefore, may contribute more to foam cell formation and atherogenesis than do the less dense LDL subfractions. 49,50 Sex differences have been noted in regard to LDL particle size. In the Framingham Study, LDL size distribution was skewed toward larger LDL particles in women (prevalence of LDL-1, 30% and of LDL-2, 31%), whereas men exhibited a more symmetric distribution (prevalence of LDL-3, 42%).…”

Section: Discussionmentioning

confidence: 99%

Frequency of ApoB and ApoE Gene Mutations as Causes of Hypobetalipoproteinemia in the Framingham Offspring Population

Welty

Lahoz

Tucker

et al. 1998

ATVB

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Abstract-Hypobetalipoproteinemia (HBLP) is characterized by plasma concentrations of apolipoprotein B (apoB) and low density lipoprotein cholesterol (LDL-C) below the fifth percentile. Some forms of HBLP have been shown to be due to truncated forms of apoB-100. A total of 3873 subjects participating in the Framingham Offspring Study had LDL-C levels measured every 4 to 5 years throughout a 25-year period. Seventy-five subjects were identified with persistent HBLP, defined as an LDL-C Ͻ70 mg/dL on at least 2 observations, for a prevalence of 1.9% in this population. Compared with subjects with LDL-C Ն70 mg/dL, subjects with HBLP had significantly lower mean levels of total cholesterol, LDL-C, triglyceride, and apoB; higher levels of high density lipoprotein cholesterol; and a higher prevalence of the E2/E3 genotype: 38.7% versus 10.9% (PϽ0.001). Men with HBLP had a larger mean LDL particle size than did men with an LDL-C Ն70 mg/dL. One individual had a truncated apoB as a cause of HBLP, for a prevalence of 0.03%. Medical causes of HBLP included 2 cases of Crohn's disease, 1 of hemochromatosis, and 1 of hepatitis. Three subjects with HBLP developed coronary heart disease, for an incidence of 4% compared with 5% in those with an LDL-C Ն70 mg/dL (PϭNS). The incidence of cancer was 8% in those with HBLP compared with 4% in those with an LDL-C Ն70 mg/dL (Pϭ0.21). In conclusion, a truncated apoB was a rare cause of HBLP, whereas the E2/E3 genotype was a much more common cause. A large prospective study is needed to evaluate the incidence of cancer and atherosclerosis in subjects with HBLP. (Arterioscler Thromb Vasc Biol. 1998;18:1745-1751.)

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Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects.

Cited by 660 publications

References 51 publications

Lipid peroxidation and susceptibility of low‐density lipoprotein to in vitro oxidation in hyperhomocysteinaemia

Lipid peroxidation and susceptibility of low‐density lipoprotein to in vitro oxidation in hyperhomocysteinaemia

Diabetic dyslipidaemia: from basic research to clinical practice*

Frequency of ApoB and ApoE Gene Mutations as Causes of Hypobetalipoproteinemia in the Framingham Offspring Population

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