Quantitative studies of ver low densit lipoprotein: conversion to low densit lipoprotein in normal controls and primar hperlipidaemic states and the role of direct secretion of low densit lipoprotein in heterozgous familial hpercholesterolaemia

Janus, Edward; Nicoll, A.; Wootton, Richard; Turner, Peter R.; Magill, Peter J.; Lewis, Barry

doi:10.1111/j.1365-2362.1980.tb02075.x

Cited by 145 publications

(56 citation statements)

References 45 publications

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“…The actual mechanism for the conversion of IDL to LDL is not known, but it may involve the hepatic LDL receptor to which IDL binds avidly (Brown & Goldstein, 1983). In normal humans, all LDL is derived from VLDL by intravascular conversion (Janus et al 1980). LDL delivers its cholesterol to cells by way of a specific LDL receptor which is present in the cell membrane.…”

Section: Ldlmentioning

confidence: 99%

The Influence of Legume Seeds on Human Plasma Lipid Concentrations

Kingman

1991

Nutr. Res. Rev.

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Section: Ldlmentioning

confidence: 99%

The Influence of Legume Seeds on Human Plasma Lipid Concentrations

Kingman

1991

Nutr. Res. Rev.

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“…29 Although this pathway may not be important in normal subjects, it assumes a significant role in patients with familial hypercholesterolemia 711 and in some patients with FCHL or unclassified hyperlipidemia. 7 Our results show that in FCHL, direct secretion of apo B into LDL accounts for a variable proportion (0% to 56%) of total LDL apo B synthesis and that the magnitude of this pathway varies according to the phenotype of the disease. Whereas in Type IV almost all of the LDL apo B was derived from VLDL, in Type lla and Mb a significant proportion of apo B was directly synthesized into LDL.…”

Section: Discussionmentioning

confidence: 93%

“…4 ' 6 Less than 50% of VLDL apo B is converted to LDL, and most of the VLDL apo B is presumably removed from plasma as remnant particles. 6 ' 7 In familial hypercholesterolemia, VLDL apo B synthesis is usually normal, 5 while LDL synthesis is on the high side of normal or increased. LDL fractional removal rate, however, is markedly reduced.…”

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confidence: 99%

Low density lipoprotein metabolism in familial combined hyperlipidemia. Mechanism of the multiple lipoprotein phenotypic expression.

Kissebah¹,

Alfarsi²,

Evans³

1984

Arteriosclerosis

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Plasma low density lipoprotein (LDL) kinetics and their relation to plasma very low density lipoprotein (VLDL) and LDL composition were determined in patients with familial combined hyperlipidemia (FCHL) of varying lipoprotein phenotypes. In both Type II and IV subjects, LDL apolipoprotein B (apo B) synthesis was greater than normal. In Type IV, the VLDL triglyceride/apo B ratio was normal and almost all of the LDL apo B was derived from VLDL. LDL cholesterol/apo B ratio was diminished and LDL apo B fractional catabolic rate (FCR) was sufficiently increased to prevent a rise in plasma LDL concentration. In Type II, VLDL triglyceride/apo B was reduced and 14% to 50% of the LDL was formed by direct synthesis. LDL cholesterol/apo B was normal and LDL apo B FCR was lower than in Type IV subjects. In four patients whose plasma lipid levels became normal with carbohydrate restriction and intake of a fibric acid derivative, plasma VLDL and LDL composition and LDL kinetic measurements remained unchanged. By contrast, VLDL triglyceride-apo B decreased and direct LDL syntheseis increased in four patients whose phenotype changed to Type Ha. LDL cholesterol/apo B also increased and LDL FCR declined. Among patients with FCHL, significant correleations between VLDL triglyceride/apo B, LDL apo B derived by direct synthesis, LDL cholesterol/apo B, and LDL apo B FCR were found. Thus, increased apo B synthesis is a characteristic feature of FCHL. The phenotypic expression is determined by the availability of triglyceride for hepatic coupling to apo B which could influence the source, composition, and removal rate of circulating LDL. Despite normalization of their plasma lipid levels, some patients continued to show the compositional and kinetic features of FCHL. (Arteriosclerosis 4:614-624, November/December 1984)

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“…Labelled lipoproteins were processed as previously described. 24 For metabolic studies labelled VLDL and LDL were injected i.v. into five hypercholesterolemic and four age-and weight-matched normolipidemic recipients via a marginal ear vein by use of a 25-gauge cannula which was then flushed with isotonic saline.…”

mentioning

confidence: 99%

“…Apo B was isolated from these fractions for specific activity measurements as previously described. 24 Apo B was isolated by tetramethylurea precipitation 25 and after solubilization in 0.5 molar NaOH, was quantified by the Lowry method using bovine albumin as the primary standard. Radioactivity was measured in an LKB twin channel counter.…”

mentioning

confidence: 99%

Hereditary hyperlipidemia in the rabbit due to overproduction of lipoproteins. I. Biochemical studies.

Ville¹,

Turner²,

Pittilo³

et al. 1987

Arteriosclerosis

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An inherited metabolic disorder in a strain of New Zealand White rabbits, characterized by marked hypercholesterolemia (394 ± 1 0 0 mg/dl), with moderately elevated or normal triglyceride levels is described. Low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and very low density lipoprotein (VLDL) cholesterol levels were increased. VLDL and IDL, and to a lesser extent LDL, had increased free cholesterol and esterified cholesterol content, and triglyceride content was reduced. Kinetic studies with 131 I and 125 l-labelled rabbit lipoproteins showed a marked increase in production rates of VLDL apo B and LDL apo B. LDL cholesterol levels were directly related to LDL apo B production rate (r = 0.938, p < 0.001). Both in hypercholesterolemic and normal rabbits injected with labelled VLDL, the specific activity-time curves of VLDL apo B and LDL apo B did not intersect, indicating that LDL apo B was in part derived from sources other than VLDL. No defect was demonstrated in receptormediated catabolism of LDL by cultured skin fibroblasts from hyperlipidemic animals. The fractional catabolic rate of LDL apo B was subnormal, but increased when the expanded LDL apo B pool size was reduced by exchange transfusion; the low fractional catabolism may therefore be attributable, at least in part, to saturation of LDL receptors consequent upon the increased pool size of LDL. The hyperlipidemia in this strain of rabbits may be unique in that the underlying mechanism appears to be overproduction of VLDL and LDL. (Arteriosclerosis 7:105-112, March/April 1987) E xperimental induction of hyperlipidemia with consequent atherosclerosis-like lesions was first documented in cholesterol-fed rabbits more than seventy years ago. 1 This and subsequent dietary studies have provided insights into the pathogenesis of atherosclerosis in humans. More recently two genetic disorders associated with atherosclerosis have been described in laboratory animals. One, in the Watanabe heritable hyperlipidemic (WHHL) rabbit, is associated with pronounced hyperlipidemia in normally fed rabbits 2 and results from a defect in receptor-mediated catabolism of low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL). 3 There is secondary overproduction of LDL. 4 ' 5 IDL and LDL levels in plasma are greatly increased. The disorder, which is associated with arterial lesions similar to human atherosclerosis, is in most respects analogous to familial hypercholesterolemia in man. The second disorder is the result of selected inbreeding to produce animals that develop pronounced hyperlipidemia and arterial lesions in response to cholesterol feeding ("hyper-responders"), reflecting a genetic predisposition to the metabolic effects of this diet. 6 Pronounced hypercholesterolemia in a chow-fed New Zealand White rabbit was observed by one of us (ALV). The rabbit was mated with a normal female; four of the first litter of seven were hypercholesterolemic. The disorder has been transmitted vertically t...

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Quantitative studies of ver low densit lipoprotein: conversion to low densit lipoprotein in normal controls and primar hperlipidaemic states and the role of direct secretion of low densit lipoprotein in heterozgous familial hpercholesterolaemia

Cited by 145 publications

References 45 publications

The Influence of Legume Seeds on Human Plasma Lipid Concentrations

The Influence of Legume Seeds on Human Plasma Lipid Concentrations

Low density lipoprotein metabolism in familial combined hyperlipidemia. Mechanism of the multiple lipoprotein phenotypic expression.

Hereditary hyperlipidemia in the rabbit due to overproduction of lipoproteins. I. Biochemical studies.

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