Sterol synthesis in vitro in freshly isolated blood mononuclear leukocytes from familial hypercholesterolemic patients treated with probucol

McNamara, Donald J.; Bloch, C; Botha, Anthea; Mendelsohn, D

doi:10.1016/0005-2760(85)90098-0

Cited by 36 publications

(13 citation statements)

References 11 publications

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“…The rate of cholesterol biosynthesis by MNC was determined as described by McNamara et al (1985). Brie¯y, MNC were incubated with 2.5 mM (2-14 C) acetate (DuPont NEN) and autologous serum obtained at the time of the test at 37 C for 4 h in a metabolic shaker.…”

Section: Cholesterol Biosynthesis In Mncmentioning

confidence: 99%

Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism

et al. 1999

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Objectives: To determine relative effects of diets high in synthetic sources of myristic (14:0), palmitic (16:0) or stearic (18:0) acid on concentrations and metabolism of serum lipoproteins. Design: Eighteen healthy women participated in a three-way cross-over study for ®ve week periods separated by seven week washout periods, diets were assigned in random order. Subjects: Premenopausal women, not on medication, were from three races (Caucasian, African-American, Asian) and four apolipoprotein E phenotype groups (3a3, 3a2, 4a3, and 4a2). Intervention: During the ®rst week the subjects consumed a baseline diet providing 11 energy (en)% saturated fat, 10 en% polyunsaturated fat and 14 en% monounsaturated fat. Followed by test diets with 19 en% saturated fat (including 14 en% test saturated fatty acid), 3 en% polyunsaturated fat, and 14 en% monounsaturated fat for four weeks. Synthetic fats (trimyristin, tripalmitin, and tristearin) were used in blends with natural fats and oils. Results: Mean concentrations of serum total, esteri®ed and LDL cholesterol were signi®cantly lower after 18:0 than after 16:0 (n 16 ± 18, P`0.01 for treatment effect). Myristic acid (14:0) had an intermediate effect.Receptor-mediated degradation of 125 I-LDL in mononuclear cells obtained from the subjects was lower after 16:0 than after 14:0 and 18:0 (n 16 ± 18, P 0.05 for treatment effect). Differences in the digestibilities of the fats were not a major factor in the results. Strong cholesterolemic responses to the 16:0 diet were partly explained by apoE phenotype. Conclusions: As noted previously, stearic acid was neutral compared to 14:0 and 16:0. In contrast to studies involving natural fats, 14:0, fed as a synthetic triglyceride, was less cholesterolemic than 16:0 in a majority of subjects. ApoE phenotype in¯uenced the cholesterolemic response particularly when diets high in 16:0 were eaten.

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Section: Cholesterol Biosynthesis In Mncmentioning

confidence: 99%

Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism

et al. 1999

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“…Over the past five years technical developments have made it possible to study cholesterol homeostasis in free-living outpatients by a combination of three procedures: (a) refinement in measurement of dietary cholesterol intake using dietary records (45); (b) quantitation of the absorption of dietary cholesterol by the isotope ratio method (46)(47)(48); and (c) analysis of changes in the rate of endogenous cholesterol synthesis by assay of sterol synthesis rates in freshly isolated peripheral blood mononuclear leukocytes (MNL) (49)(50)(51).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.

McNamara¹,

Kolb²,

Parker³

et al. 1987

J. Clin. Invest.

281

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Studies were carried out to examine the effects of dietary fat and cholesterol on cholesterol homeostasis in man. 75 12-wk studies were carried out during intake of 35% of calories as either saturated or polyunsaturated fat, first low and then high in dietary cholesterol. Dietary fat and cholesterol intakes, plasma lipid and lipoprotein levels, cholesterol absorption and sterol synthesis in isolated blood mononuclear leukocytes were measured during each diet period. In 69% of the studies the subjects compensated for the increased cholesterol intake by decreasing cholesterol fractional absorption and/or endogenous cholesterol synthesis. When an increase in plasma cholesterol levels was observed there was a failure to suppress endogenous cholesterol synthesis. Plasma cholesterol levels were more sensitive to dietary fat quality than to cholesterol quantity.The results demonstrate that the responses to dietary cholesterol and fat are highly individualized and that most individuals have effective feedback control mechanisms.

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“…Previous studies have shown that isolated monocytes can be used as a marker of cholesterol and LDL metabolism (33,34).…”

Section: Discussionmentioning

confidence: 99%

Increased metabolism of peroxynitrite‐modified [125I] β‐VLDL by monocytes from hypercholesterolemic rabbits

Silva

Abdalla

1998

IUBMB Life

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SummaryThe metabolism (uptake and degradation) of peroxynitrite-modified 13-VLDL and native 13-VLDL labeled with [t251]iodine was studied in monocytes isolated from peripheral blood of hypercholesterolemic (HC) and normolipidemic rabbits (NC). The peroxynitrite-modified 13-VLDL uptake and degradation was up to 2-fold higher in monocytes from HC rabbits than monocytes from NC rabbits. In addition, monocytes from HC rabbits took up and degraded significantly more peroxynitrite-modified 13-VLDL than native 13-VLDL. In contrast, monocytes from NC rabbits took up both lipoproteins in a similar rate and degraded more native 13-VLDL than peroxynitrite-modified 13-VLDL. Our results suggest that hypercholesterolemia can affect monocyte metabolism enhancing foam cell formation by increasing the influx of peroxynitrite-modified 13-VLDL.

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Sterol synthesis in vitro in freshly isolated blood mononuclear leukocytes from familial hypercholesterolemic patients treated with probucol

Cited by 36 publications

References 11 publications

Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism

Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism

Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.

Increased metabolism of peroxynitrite‐modified [125I] β‐VLDL by monocytes from hypercholesterolemic rabbits

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