Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia

Napoli, Claudio; Ambrosio, Giuseppe; N, Scarpato; Corso, Gaetano; Palumbo, Giuseppe; D’Armiento, Francesco Paolo; Mancini, Francesco Paolo; Malorni, Antonio; Formisano, S; Ruocco, Antonio; Calì, A; Chiariello, Massimo

doi:10.1016/s0002-8703(97)70155-8

Cited by 65 publications

(60 citation statements)

References 48 publications

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“…The formation of thiobarbituric acid reactive substances was determined by the thiobarbituric acid method (50). Lipid peroxides, measured by the LPO colorimetric kit (Kamiya Biomedical, Thousand Oaks, CA) (50), were assayed in cell sonicates of mouse peritoneal macrophages isolated from the peritoneal fluid, as described (55,56). Isoprostane 8-epi-PGF 2␣ purified from plasma samples was measured by using an immunoassay (Cayman Chemical, Ann Arbor, MI) (50,57).…”

Section: Evaluation Of Oxidative Stress and Nitrite And Nitrate (Nox)mentioning

confidence: 99%

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Napoli

Williams-Ignarro

Nigris

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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105

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CorrectionsPHARMACOLOGY. For the article ''Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress,'' by Filomena de Nigris, Lilach O. Lerman, Sharon Williams Ignarro, Giacomo Sica, Amir Lerman, Wulf Palinski, Louis J. Ignarro, and Claudio Napoli, which appeared in issue 3, February 4, 2003, of Proc. Natl. Acad. Sci. USA (100, 1420-1425 first published January 13, 2003; 10.1073͞pnas.0237367100), the authors should have noted that Louis J. Ignarro developed and markets Niteworks, a dietary supplement of L-arginine, L-citrulline, vitamin E, and vitamin C. Dr. Ignarro is also a member of the Scientific Advisory Board of Herbalife, the distributor of Niteworks. The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (L-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and L-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with L-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.catalase ͉ nitric oxide synthase ͉ vitamin E ͉ oxidative stress ͉ low-density lipoprotein P hysical exercise is a deterrent of cardiovascular disease and atherogenesis in animal models (1-5). Exercise can also positively influence classical risk factors that are associated with coronary heart disease such as diabetes, hypertension, obesity, dyslipidemias, and endothelial dysfunction (6-8). The higher respiration rate during severe physical exercise leads to the generation of more free radicals than the endogenous antioxidant systems can scavenge (9), whereas moderate intensity aerobic exercise enhances endothelium dependent vasodilation in humans (10), and attenuates exercise-induced peroxidation (11) and cardiovascular mortality (12) in the elderly. Moreover, there is an inverse association between intensity of physical activity and the risk of coronary heart disease events (13). A metaanalysis of 51 con...

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Section: Evaluation Of Oxidative Stress and Nitrite And Nitrate (Nox)mentioning

confidence: 99%

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Napoli

Williams-Ignarro

Nigris

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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105

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“…To investigate the correlation of fetal cholesterol levels with maternal cholesterol levels and fetal age, only data from fetal blood samples obtained before death were used. Lipoperoxide levels in EDTA-containing plasma were evaluated spectrophotometrically using the LPO kit (Kamiya Biomedical Company, Thousand Oaks, CA) as previously described (31,32).…”

Section: Methodsmentioning

confidence: 99%

“…Because hypercholesterolemia is a well-recognized risk factor of atherogenesis and because it enhances LDL oxidation in humans (30)(31)(32), we used fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia during pregnancy in addition to normocholesterolemic mothers. In doing so, this study also provides the first systematic morphometric assessment of fatty streak development in fetal aortas, and yields information on the role of maternal and fetal hypercholesterolemia in fetal fatty streak formation.…”

Section: Introductionmentioning

confidence: 99%

Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.

Napoli¹,

D’Armiento²,

Mancini³

et al. 1997

J. Clin. Invest.

868

584

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To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2 Ϯ 1.3 mo). For this purpose, a systematic assessment of fatty streak formation was carried out in fetal aortas from normocholesterolemic mothers ( n ϭ 22), hypercholesterolemic mothers ( n ϭ 33), and mothers who were hypercholesterolemic only during pregnancy ( n ϭ 27). Fetal plasma cholesterol levels showed a strong inverse correlation with fetal age ( R ϭ Ϫ 0.88, P Ͻ 0.0001). In fetuses younger than 6 mo, fetal plasma cholesterol levels correlated with maternal ones ( R ϭ 0.86, P ϭ 0.001), whereas in older fetuses no such correlation existed. Fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia contained significantly more and larger lesions (758,651 Ϯ 87,449 and 451,255 Ϯ 37,448 m 2 per section, respectively; mean Ϯ SD) than aortas from normocholesterolemic mothers (61,862 Ϯ 9,555 m 2 ; P Ͻ 0.00005). Serial sections of the arch, thoracic, and abdominal aortas were immunostained for recognized markers of atherosclerosis: macrophages, apo B, and two different oxidation-specific epitopes (malondialdehyde-and 4-hydroxynonenal-lysine). Of the atherogenic sites that showed positive immunostaining for at least one of these markers, 58.6% were established lesions containing both macrophage/foam cells and oxidized LDL (OxLDL). 17.3% of all sites contained only native LDL, and 13.3% contained only OxLDL without monocyte/ macrophages. In contrast, only 4.3% of sites contained isolated monocytes in the absence of native or oxidized LDL. In addition, 6.3% of sites contained LDL and macrophages but few oxidation-specific epitopes. These results demonstrate that LDL oxidation and formation of fatty streaks occurs already during fetal development, and that both phenomena are greatly enhanced by maternal hypercholesterolemia. The fact that in very early lesions LDL and Ox-LDL are frequently found in the absence of monocyte/macrophages, whereas the opposite is rare, suggests that intimal LDL accumulation and oxidation contributes to monocyte recruitment in vivo. ( J. Clin. Invest. 1997. 100:2680-2690.)

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“…Oxygen radicals generated by the X/XO reaction can modify LDL. 8,31,35 In vitro, X/XO generates a peak of oxygen radicals within the range that can be encountered in vivo and similar to that released by arterial wall cells, fibroblasts, and mesangial cells. 35 The fact that XO activity is present in human atherosclerotic plaques 36 further supports the role of X/XO-induced radical generation in humans.…”

Section: Plasma and Ldl Oxidationmentioning

confidence: 97%

“…31 LDL was isolated by 2 consecutive steps of discontinuous density ultracentrifugation in a KBr gradient, as previously described in detail. 32 A Sephacryl S-300 column (5ϫ0.9 cm, equilibrated with 150 mmol/L NaCl-PBS, 1 mmol/L EDTA) was used both to desalt and to remove lowmolecular-weight components from the samples, and LDL was used within a few hours to prevent spontaneous oxidation.…”

Section: Plasma and Ldl Oxidationmentioning

confidence: 99%

1,4-Dihydropyridine Calcium Channel Blockers Inhibit Plasma and LDL Oxidation and Formation of Oxidation-Specific Epitopes in the Arterial Wall and Prolong Survival in Stroke-Prone Spontaneously Hypertensive Rats

Napoli

Salomone

Godfraind

et al. 1999

Stroke

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Background and Purpose-Calcium-channel blockers (CCBs) reduce systolic blood pressure and stroke-related mortality in stroke-prone spontaneously hypertensive rats (SPSHR). Brain ischemia is associated with loss of intracellular antioxidants. Increased formation of oxygen radicals and oxidation of LDL may enhance arterial vasoconstriction by various mechanisms. CCBs that also exert antioxidative properties in vitro may therefore be particularly useful. To investigate such antioxidant effects in vivo, we determined several parameters of LDL oxidation in SPSHR treated with two 1,4-dihydropyridine-type (1,4-DHP) CCBs of different lipophilic properties and compared them with antioxidanttreated and untreated controls. We also tested whether these drugs decrease the formation of oxidation-specific epitopes in arteries. Methods-Five groups of 9 to 14 SPSHR each (aged 8 weeks) were treated with 80 mg/kg body wt per day nifedipine, 1 mg or 0.3 mg/kg body wt per day lacidipine, vitamin E (100 IU/d), or carrier for 5 weeks. A group of Wistar-Kyoto rats was used as normotensive control. Plasma samples were taken, and LDL was isolated by ultracentrifugation. Then LDL was exposed to oxygen radicals generated by xanthine/xanthine oxidase reaction (2 mmol/L xanthineϩ100 mU/mL xanthine oxidase), and several parameters of oxidation were determined. The presence of native apolipoprotein B and oxidation-specific epitopes in the carotid and middle cerebral arteries was determined immunocytochemically. Results-1,4-DHP CCBs completely prevented mortality. Normotensive Wistar-Kyoto rats showed less oxidation than control SPSHR. Plasma lipoperoxide levels were 0.87Ϯ0.27 mol/L in control SPSHR, 0.69Ϯ0.19 and 0.63Ϯ0.20 mol/L in the groups treated with 0.3 and 1 mg lacidipine, respectively, and 0.68Ϯ0.23 mol/L in nifedipine-treated animals (PϽ0.05 versus control SPSHR for all values). Both CCBs significantly decreased formation of conjugated dienes and prolonged the lag time in LDL exposed to oxygen radicals. Similarly, lipoperoxides and malondialdehyde were significantly reduced (PϽ0.05). Reduced relative electrophoretic mobility and increased trinitrobenzenesulfonic acid reactivity of LDL from treated rats (PϽ0.01) also indicated that fewer lysine residues of apolipoprotein B were oxidatively modified in the presence of 1,4-DHP CCBs. Finally, these drugs reduced the intimal presence of apolipoprotein B and oxidized LDL (oxidation-specific epitopes) in carotid and middle cerebral arteries. Conclusions-In the SPSHR model, 1,4-DHP CCBs reduce plasma and LDL oxidation and formation of oxidation-specific epitopes and prolong survival independently of blood pressure modifications. Our results support the concept that the in vivo protective effect of these drugs on cerebral ischemia and stroke may in part result from inhibition of oxidative processes. (Stroke. 1999;30:1907-1915

show abstract

Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia

Cited by 65 publications

References 48 publications

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.

1,4-Dihydropyridine Calcium Channel Blockers Inhibit Plasma and LDL Oxidation and Formation of Oxidation-Specific Epitopes in the Arterial Wall and Prolong Survival in Stroke-Prone Spontaneously Hypertensive Rats

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