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Biomedical subjects

G Schonfeld

Publications and source records attributed to G Schonfeld.

At least 55 records · Page 3Linked to original sources
PubMed1995

Genetic variation of apolipoprotein B can produce both low and high levels of apoB-containing lipoproteins in plasma.

The polymorphic markers of the apolipoprotein B (apoB) gene include restriction fragment length polymorphisms (RFLPs) scattered along the length of the gene, an insertion/deletion (I/D) polymorphism at the 5' and variable numbers of tandem repeats (VNTRs) at the 3' untranslated ends. The Xbal and I/D polymorphisms which do not affect apoB structure, produce modest effects on fasting and postprandial lipids and on responsiveness to dietary lipids, but the effects are population, age and gender-dependent. Much larger effects on fasting lipid levels are produced by structural mutations of the apoB gene. The apoB 3500 mutation affecting the low density lipoprotein (LDL) receptor recognition region of apoB-100, is one of the causes of the autosomal codominant familial hypercholesterolemia phenotype, characterized by fasting LDL elevations and atherosclerosis. Neither fasting nor postprandial hypertriglyceridemia are consistently present. Some forms of familial hypobetalipoproteinemia (FHBL) are genetically linked to various truncation-producing mutations of the gene. To date approximately 30 deletion, insertion or non-sense mutations have been identified resulting in apoB truncations ranging in size from apoB-9 to apoB-89. FHBL segregates as an autosomal dominant trait. Heterozygotes have less than a 5th to 10th percentile levels while compound heterozygotes and true homozygotes have much less than 5th percentile levels of total and LDL cholesterol. Heterozygotes have no symptoms traceable to the gene defect. Alterations in the distributions of apoB truncations among the lipoproteins in plasma and in the metabolism of the lipoproteins containing apoB-truncations depend on the lengths of the truncations.

Apolipoproteins B↗
PubMed1995

Regulation of low density lipoprotein receptor gene expression in HepG2 and Caco2 cells by palmitate, oleate, and 25-hydroxycholesterol.

Our in vivo studies in mice have shown that LDL-receptor gene expression is regulated differently in both liver and intestine by dietary cholesterol and dietary saturated fat. While dietary cholesterol serves to regulate at transcriptional levels, dietary fatty acids do not. To study the mechanism of regulation of LDL-receptor by saturated fat and cholesterol at the cellular level, where any secondary effects of long-term feeding in vivo are minimized we used the cultured hepatoma and colon carcinoma cells, HepG2 and Caco2. LDL-receptor activity was determined by 125I-labeled LDL binding and uptake, LDL-receptor protein by Western blotting, LDL-receptor mRNA by RNase protection assay, and relative rates of LDL-receptor mRNA transcription by nuclear 'run-off' assay. Incubation of cells in lipoprotein-deficient serum (LPDS) for 48 h progressively induced LDL-receptor activity and LDL-receptor protein by 5- to 6-fold in HepG2 cells and 2- to 3-fold in Caco2 cells. Absolute levels of LDL-receptor mRNA and relative rates of LDL-receptor mRNA transcription also increased in parallel to the LDL-receptor activity and protein levels in both cell lines. These data suggest that LPDS induced the LDL-receptor gene by transcriptional mechanism. The suppressive effect of 25-hydroxycholesterol on LDL-receptor regulation was studied by incubating HepG2 and Caco2 cells grown either in 10% FCS or 10% LPDS for 24 h and then for 0-24 h with various doses of 25-hydroxycholesterol. In HepG2 cells, LDL-receptor activity and protein mass progressively decreased to 50% of zero time controls over 24 h. LDL-receptor mRNA levels and relative rates of transcription decreased in parallel. In Caco2 cells, 25-hydrocholesterol lowered LDL-receptor activity, mRNA, and transcription by approximately 35%. To examine the effects of palmitate on LDL-receptor regulation, palmitate was complexed with albumin. Palmitate decreased LDL-receptor activity by 25% in HepG2 cells without altering LDL-receptor mass, mRNA levels, or rates of mRNA transcription. Similarly, in Caco2 cells, palmitate decreased LDL-receptor activity and protein mass 30% of controls, but did not change LDL-receptor mRNA levels and/or rates of transcription. The combination of palmitate (0.8 mM) and 25-hydroxycholesterol (2.5-5 micrograms/ml) suppressed LDL-receptor activity by 65% in HepG2 cells and by 52% in Caco2 cells. However, LDL-receptor mRNA decreased by approximately 50% in HepG2 cells and 30-40% in Caco2 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood↗
PubMed1995

Physiologic mechanisms of action of lovastatin in nephrotic syndrome.

The effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the metabolism of apolipoprotein (apo) B-containing lipoproteins appear to differ according to the predominant lipoprotein profiles present and the condition being treated. In familial hypercholesterolemia, with isolated low density lipoprotein (LDL) elevations, the LDL-apoB elimination rate is increased by up-regulated LDL-receptors. In familial combined hyperlipidemia where very low density lipoprotein (VLDL) and LDL both may be increased and enhanced production of LDL-apoB may be present, HMG-CoA reductase inhibitors seem to diminish increased LDL-apoB production. The drug-induced decreases in LDL-apoB production could be due to decreased production of precursor VLDL-apoB or due to decreased conversion of VLDL-apoB to LDL-apoB after enhanced removal of VLDL by up-regulated LDL-receptors. To distinguish between these possibilities, we assessed the effects of HMG-CoA reductase inhibitors in another condition in which there is both apoB overproduction and accumulation of VLDL and LDL in plasma, the nephrotic syndrome. We used endogenous labeling of apoB with [13C]leucine and a multicompartmental model to calculate the metabolic parameters of apoB-containing lipoproteins. Only subjects with focal segmental glomerular sclerosis (FSGS) were included, as FSGS is a chronic, very slowly progressive form of nephrotic syndrome. A double-blind, randomized, placebo-controlled, crossover design was used. Treatment periods of 6 weeks were separated by a 2-week washout period. Of the four men studied, three had high triglyceride levels and four had high cholesterol levels. Lovastatin (20 mg/day) significantly decreased cholesterol (27.6 +/- 6%), LDL-cholesterol (27.6 +/- 9%) and plasma apoB (17.9 +/- 2.9%) (P < 0.01 for all). During the placebo period, calculation of kinetic parameters revealed VLDL-, intermediate density lipoprotein (IDL)-, and LDL-apoB overproduction and decreased VLDL-apoB fractional catabolic rate. Lovastatin significantly decreased LDL-apoB production rate in all cases (34.1 +/- 14%, P = 0.03). The decreased LDL-apoB was mainly due to a channelling of LDL precursors away from conversion to LDL (conversion of VLDL to LDL decreased from 80.6 +/- 8.3% to 55.9 +/- 17.2%, P = 0.05). Thus, lovastatin decreased LDL-cholesterol in nephrotic subjects mainly by inhibiting LDL-apoB production from VLDL.

Apolipoproteins↗
PubMed1994

Regulation of the apolipoprotein AIV gene expression by estrogen differs in rat and mouse.

Previously we have shown that estrogen administration to Sprague Dawley rats and to the inbred C3H/HeJ mouse strain produced different effects on plasma lipoproteins [Srivastava, R. A. K., Baumann, D. & Schonfeld, G. (1993) Eur. J. Biochem. 216, 527-538]. While low-density lipoprotein (LDL) levels fell in rats, they rose in mice. Plasma apoprotein (apo) AI levels and high-density lipoprotein (HDL) cholesterol fell in both species but by much less in mice than in rats. Since apolipoproteins AIV and AII are two other protein constituents of HDL, we wished to test the hypothesis that estrogen would produce different effects on these apoproteins in mice and rats. Male rats and C3H/HeJ mice were administered 17 beta-estradiol at 5 micrograms.g body mass-1.day-1 for six consecutive days. In a separate experiment, castrated male C3H/HeJ mice were administered beta-estradiol [(0.16 micrograms.g body mass-1.day-1 or 5.0 micrograms.g body mass-1.day-1, or testosterone (1 microgram/g)] for 14 days. ApoAIV mRNA levels were determined in total liver, in liver nuclei and in total intestine. Rat hepatic apoAIV mRNA decreased twofold (from 16.5 +/- 3 pg/micrograms total RNA to 7.1 +/- 2.5 pg/micrograms total RNA) while mouse hepatic and nuclear apoAIV mRNA both increased 1.5-2-fold. Intestinal apoAIV mRNA decreased in mice and increased in rats. Testosterone had no effects. Nuclear apoAIV mRNA transcription rates in rat and mouse liver changed little, if at all, indicating that estrogen-induced changes in steady-state levels of apoAIV mRNA were not determined by hepatic transcriptional mechanisms. Both species possessed similar apoAIV mRNA transcription start sites. To assess whether other mouse strains also differed from rats, we surveyed 13 other inbred mouse strains. Some strains increased hepatic apoAIV mRNA, some did not change but, in contrast to rat, no strain experienced a fall in mRNA levels. Estrogen-induced changes in plasma apoAIV levels were not correlated with changes in the levels of hepatic apoAIV mRNA levels. These data indicate that (a) apoAIV mRNA levels are regulated differently by estrogen in mouse and rat livers and intestines, (b) regulation of apoAIV mRNA by estrogen is both mouse strain and tissue specific and (c) regulation of plasma apoAIV is achieved by mechanisms other than those depending on the steady-state levels of hepatic apoAIV mRNA. In contrast with apoAIV mRNA, estrogen decreased hepatic apoAII mRNA both in rat (threefold) and in mouse (twofold) and parallel changes were observed in transcription rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Recent concepts of lipoprotein pathophysiology.

Molecular genetic approaches have added greatly to the understanding of the human hyperlipoproteinemias. Studies in mice have added interesting new information. Transgenic mice over-expressing or deficient in various individual proteins important in lipoprotein metabolism have reproduced some dyslipidemias and permitted further pinpointing of the functions of apolipoproteins, lipoprotein receptors, lipid transfer proteins and enzymes. Cross-breeding of mice with single defects has reproduced certain dyslipidemia syndromes and permits examination of the combined etiologic effects of more than one gene.

Animals↗
PubMed1994

The role of cholesterol accumulation in prosthetic vascular graft anastomotic intimal hyperplasia.

PURPOSE: To demonstrate that modulation of plasma cholesterol concentrations affects prosthetic vascular graft anastomotic intimal hyperplasia (AIH), aortic grafts were examined histologically and biochemically in 41 rabbits. METHODS: Twenty-seven rabbits were fed standard rabbit diet, whereas 14 were fed cholesterol-supplemented diet to induce hypercholesterolemia. RESULTS: A smooth muscle cell proliferative response, similar to AIH in humans, was seen equally at the proximal and distal anastomoses. However, surface area and thickness of AIH were significantly greater in rabbits with hypercholesterolemia. Anastomotic tissue cholesterol concentrations were fifteenfold higher in rabbits with hypercholesterolemia than in rabbits with normal cholesterol concentrations and anastomotic cholesterol concentrations were fivefold higher than in the aorta away from the graft in rabbits with hypercholesterolemia. Preferential deposition of radioiodinated dilactitol tyramine coupled to low-density lipoproteins, but not albumin, was demonstrated in anastomotic areas and grafts of rabbits with normal cholesterol concentrations as well. Surface area and thickness of AIH correlated closely with plasma and tissue cholesterol concentrations. CONCLUSIONS: Oxidized products of lipoproteins have been shown to stimulate production of growth factors that cause smooth muscle cell proliferation, migration, and synthetic function. It is likely they play an important part in prosthetic vascular graft AIH, similar to their role in atherogenesis.

Anastomosis, Surgical↗
PubMed1994

Probucol reduces the cellularity of aortic intimal thickening at anastomotic regions adjacent to prosthetic grafts in cholesterol-fed rabbits.

Intimal hyperplasia is a persistent problem after implantation of prosthetic grafts. Although the mechanisms underlying this hyperplastic response are unknown, it has been proposed that such responses may be due to chronic vascular injury similar to that of atherogenesis. Thus, the role of oxidation was explored using the potent antioxidant drug probucol. Adult New Zealand White rabbits fed a modestly (0.25%) cholesterol-enriched diet had a polytetrafluoroethylene prosthetic graft placed into the lower aorta. After the grafting procedure, a group of 11 rabbits was placed on the cholesterol-enriched diet supplemented with 1% wt/wt probucol while a control group of 10 rabbits was placed on the cholesterol-enriched diet alone. The rabbits were maintained for a further 10 weeks before histological examination of the area surrounding the graft. Although administration of probucol did not significantly alter the dimensions of lesions at the anastomotic sites, the drug promoted striking histological changes in the surrounding tissue. Both groups of rabbits had a similar intimal hyperplastic response of the aortic tissue surrounding the graft. The vascular lesions present in the perigraft region of the control group consisted of a normal-appearing media but a thickened intima. The thickened intima contained numerous smooth muscle cells in a network of extracellular matrix. Regions in the neointima that were rich in smooth muscle cells exhibited modest staining for proliferating cell nuclear antigen. A few macrophages were present in the control group as determined by immunostaining with the monoclonal antibody RAM-11. In contrast, administration of probucol led to a marked reduction in the presence of RAM-11-staining macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1994

Dysbetalipoproteinemia in a kindred with hypobetalipoproteinemia due to mutations in the genes for ApoB (ApoB-70.5) and ApoE (ApoE2).

We identified the first insertion mutation that specifies an apolipoprotein (apo)B truncation, apoB-70.5, in a father and son with hypobetalipoproteinemia (total and low-density lipoprotein [LDL] cholesterol < 5th percentile, plasma apoB levels approximately one third of normal). The mutation is due to insertion of an adenine (A) into a 7-A repeat between cDNA position 9754 and 9760 of the apoB gene, resulting in a frame shift of 13 new amino acids and a termination codon at amino acid residue 3197. The DNA mutation cosegregated with the apoB truncation and hypobetalipoproteinemia in the kindred. The two apoB-70.5/apoB-100 heterozygotes also are apoE2 homozygotes by genotyping; beta-very-low-density lipoprotein (VLDL) was present, and VLDL cholesterol/triglyceride ratios were increased (0.29) in the plasmas of both. Density gradient ultracentrifugation and gel filtration chromatography profiles showed increased amounts of particles in the VLDL and intermediate-density lipoprotein density and size ranges and relatively smaller peaks of LDL than in controls. Two populations of LDL were present, ApoB-70.5 was primarily associated with LDL particles of higher density and of smaller size than the LDL particles containing apoB-100. ApoB-48-containing particles were present in the VLDL of fasting plasmas of both subjects, and the postprandial levels of chylomicrons and remnants as measured by the vitamin A fat tolerance test were increased. In conclusion, both subjects heterozygous for apoB-70.5 and homozygous for apoE2 showed the classic characteristics of dysbetalipoproteinemia superimposed onto the hypolipoproteinemia state.

Adult↗
PubMed1994

Donor splice mutation generates a lipid-associated apolipoprotein B-27.6 in a patient with homozygous hypobetalipoproteinemia.

We report the characterization of a new truncated apolipoprotein (apo) B, originally identified in the plasma of a homozygous proband and three heterozygous family members with hypobetalipoproteinemia. Using Western blotting, the truncated apoB species was estimated to be 27.5% the size of apoB-100. After fast protein liquid chromatography of plasma from the proband (CD) and mother (OS), the truncated apoB was eluted with particles whose sizes were between normal low and high density lipoproteins. Sequencing of exons 21-24, including the intron-exon boundaries, revealed a T-->C transition at +2 of intron 24, homozygous in CD and heterozygous in OS, thus disrupting the 5' donor splice site and interrupting the translation of serine. On the basis of this, the truncated protein was estimated to be approximately apoB-27.6. The reason for this approximation is that splice-junction mutations can generate different mRNA transcripts, and the truncated protein might represent a mixture of novel carboxy-terminal peptides, terminated by in-frame STOP codons. To date, apoB-27.6 is the smallest truncated species identified in plasma and associated with lipid. An explanation for this could be the hydrophobic nature of the novel carboxy-terminal peptides, which might enable stabilization of the particles by solubilization of sufficient lipid.

Adult↗
PubMed1994

Apolipoprotein B-38.9 does not associate with apo[a] and forms two distinct HDL density particle populations that are larger than HDL.

We have identified a new truncated apolipoprotein B (apoB) that provides insights into the interaction of apoB with apo[a] and with lipids. Both total and LDL-cholesterol were below the 5th percentile in the proband; Lp[a] was 28 mg/dl. Four other affected individuals were identified in this kindred. Immunoblotting of plasma apoB-containing lipoproteins with an anti-apoB monoclonal antibody revealed a major band for apoB-100 and a minor band with apparent M(r) 217 kDa. The apoB truncation is due to a -1 frameshift mutation, consisting of a cytosine deletion at cDNA position 5444, that results in the translation of 22 novel amino acids terminating at residue 1767. The mutation was confirmed in the affected subjects by allele-specific oligonucleotide (ASO) analysis. Gel filtration of whole plasma revealed that the minority of apoB-38.9 eluted with IDL- and LDL-sized particles, while the majority (approximately 60%) eluted between LDL and HDL. Lp[a] eluted between VLDL and LDL. Upon preparative density gradient ultracentrifugation (DGUC), the majority of the plasma apoB-38.9 (approximately 65%) floated at a density of 1.12 g/ml coincident with the major peak of HDL cholesterol. Lp[a] floated at a peak density of 1.08 g/ml between LDL and HDL. Immunoblots of the apoB-38.9-containing HDL density DGUC fractions subjected to nondenaturing gradient gel electrophoresis (GGE) demonstrated two apoB-38.9-containing particle populations with diameters of approximately 15 nm and approximately 18 nm, respectively. Lipoproteins of these sizes were also detected when whole plasma was subjected to GGE and immunoblotting. The 15-18 nm lipoproteins correspond to the gel filtration populations eluting between LDL and HDL. Lysine-Sepharose chromatography of plasma yielded retained products that contained apo[a] and apoB-100 but not apoB-38.9. Immunoprecipitation of whole plasma with monospecific polyclonal anti-human apo[a] showed apo[a] and apoB-100, but no apoB-38.9 to be present in precipitates. ApoB-100 and apoB-38.9 were present in supernates. In in vitro incubations, recombinant apo[a] formed complexes with apoB-100 but not with apoB-38.9-containing particles. Our results show that the apoB-38.9 protein can be found in a variety of lipoproteins; however, the majority of apoB-38.9-containing lipoproteins float at a density equivalent to HDL but are larger than HDL, being intermediate in size between apoB-100 LDL and HDL. The heterogeneity of apoB-38.9 lipoproteins may reflect their dual tissue source, i.e., liver and intestine, and the discordance between size and density indicates a disproportionately reduced association of lipids with apoB-38.9. Finally, our data suggest that apoB-38.9 is incapable of forming complexes with apo[a] in plasma.

Aged↗
PubMed1993

Who should treat familial hypercholesterolemia?

The treatment of various manifestations of familial hypercholesterolemia can involve a variety of health professionals over the lifetime of a given patient. The first task is to diagnose the condition. This should be done by primary physicians, i.e., pediatricians, family practitioners and internists. The same professionals, with help from dietitians as necessary, should treat the hypercholesterolemia in most cases. Homozygotes and difficult to treat heterozygotes should be referred to endocrinologists or lipidologists. The various cardiovascular manifestations, at one time or another, may require consultation with cardiologists, neurologists, radiologists, and cardiac or vascular surgeons. Physiatrists and physical and occupational therapists also may contribute to patient care.

Health Personnel↗
PubMed1993

In vivo regulation of low-density lipoprotein receptors by estrogen differs at the post-transcriptional level in rat and mouse.

Rats and mice are frequently used in studies of the regulation of lipoprotein metabolism. Although the species are closely related, they differ dramatically in the responses of their lipoproteins to estrogen administration. In rats, estrogens produce profound decreases in the levels of all plasma lipoproteins and this is attributed largely to estrogen-induced increases of hepatic low-density lipoprotein receptor (LDL-receptor) activity. Estrogens affect mouse plasma lipoproteins to a much lesser extent. Therefore, one of our aims was to compare the regulation of LDL-receptor gene expression in rats and mice at several potential loci of regulation. To assess the specificity of the estrogen effect, we also compared the responses of apolipoprotein AI (apoAI), apolipoprotein B (apoB), and beta-actin to the response of the LDL-receptor. In male Sprague Dawley rats given 17 beta-estradiol or 17 alpha-ethinyl estradiol at supraphysiological doses of 5 micrograms/g body mass/day, plasma total cholesterol and triacylglycerols fell to approximately 5% and approximately 50%, and, plasma apoAI and apoB fell to approximately 12% and approximately 16% of controls, respectively. By contrast, in male C3H/HeJ mice the above parameters dropped only to approximately 65% of controls and apoB concentrations rose to approximately 200% of controls. In rats, relative rates of LDL-receptor mRNA transcription (nuclear 'run-off' assay) and total hepatic, nuclear and polysomal LDL-receptor mRNA levels (RNase protection assay) increased by 1.5-2-fold, while synthesis of LDL-receptor protein on hepatic polysomes (in a wheat-germ translation system) increased 8-fold and LDL-receptor protein mass in hepatic plasma membranes increased 10-fold (by immunoblotting). In mouse liver, too, LDL-receptor mRNA levels increased 1.5-fold and the LDL-receptor mRNA transcription start sites in rat and mouse were found to be the same, but mouse LDL-receptor protein mass did not change, i.e. LDL-receptors of mice were similar to rat with respect to transcriptional regulation, but differed in their post-transcriptional control mechanisms. In rats, estrogen administration increased apoAI mRNA transcription rates 1.6-fold and also apoAI mRNA levels in total liver homogenates, nuclei and polysomes, (2-fold for each) consistent with transcriptional regulation. However, apoAI synthesis on total RNA increased less than apoAI mRNA, indicating that apoAI translational control mechanisms, at least in part, also regulate hepatic rates of apoAI production. ApoB mRNA transcription rates and levels showed small increases following estrogen administration. Hepatic beta-actin mRNA transcription and levels did not change.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis.

We demonstrate here that CD59, an inhibitor of the membrane attack complex (MAC) of the complement system, is present in cell-free seminal plasma (SP) at a concentration of at least 20 micrograms/ml. Analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and Edman degradation indicated that this protein, SP CD59, was similar, if not identical, to CD59 isolated from erythrocyte (E) membranes (E CD59). Like purified E CD59, SP CD59 also possesses a glycosyl phosphatidyl inositol (GPI) anchor and incorporates into the membranes of heterologous cells where it inhibits lysis by the human MAC. This phenomenon could be demonstrated not only if cells were incubated with purified SP CD59 but also if unfractionated SP were used. Further, CD59 in unfractionated SP bound to washed spermatozoa, increasing their membrane content of the protein. The mechanism by which this protein retains its GPI anchor while apparently present in the fluid phase is of interest and was further investigated. Using the techniques of high-speed centrifugation, fast performance liquid chromatography fractionation, and electron microscopy, we found that all detectable SP CD59 was associated with vesicular extracellular organelles. These organelles, named "prostasomes," were previously known to be present in SP and to interact with spermatozoa, although their function was uncertain. Interaction of heterologous E with prostasomes rendered the cells more resistant to lysis by human MACs. We propose that these organelles represent a pool of CD59 from which protein lost from spermatozoa, perhaps as a result of low level complement attack or of normal membrane turnover, can be replenished.

3T3 Cells↗
PubMed1993

Effect of pravastatin on metabolic parameters of apolipoprotein B in patients with mixed hyperlipoproteinemia.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce plasma cholesterol in different forms of hyperlipoproteinemia. Although an increase in low-density lipoprotein (LDL) receptor activity is the proven mechanism of this therapy in familial hypercholesterolemia, the mechanism remains controversial in mixed hyperlipoproteinemia. A decreased production of apolipoprotein B (apoB) and/or an increased removal of lipoproteins could mediate the hypocholesterolemic effect of these drugs. The effect of pravastatin on the metabolism of apoB was evaluated in a randomized, double blind, placebo controlled, cross-over study in five men with mixed hyperlipoproteinemia. Metabolic parameters for apoB were determined using endogenous labeling with [1-13C]leucine and [15N]glycine and multicompartmental modeling. During pravastatin therapy cholesterol, LDL cholesterol, apoB, and LDL apoB levels were significantly reduced (P < 0.01) by 18%, 20%, 27%, and 29%, respectively, while triglyceride and high-density lipoprotein cholesterol levels remained unchanged. Pravastatin therapy increased the fractional catabolic rate of very low density lipoprotein apoB from 3.9 +/- 0.6 to 5.1 +/- 1.7 per day (P = 0.08) and that of LDL apoB from 0.37 +/- 0.09 to 0.46 +/- 0.10 per day (P < 0.01). The apoB production (placebo 35.2 +/- 11.9 mg/kg per day; pravastatin 25.8 +/- 8.7 mg/kg per day) and conversion of very low density lipoprotein apoB to LDL apoB (placebo 65%, pravastatin 57%) remained stable. Thus, also in mixed hyperlipoproteinemia 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the catabolism of apoB-containing lipoproteins without significantly affecting the production of apoB.

Adult↗
PubMed1993

Exercise training decreases plasma cholesteryl ester transfer protein.

To assess the effect of exercise on the plasma concentration of cholesterol ester transfer protein (CETP) and its possible influence in mediating the exercise-associated redistribution of cholesterol among plasma lipoproteins, we measured plasma CETP in 57 healthy normolipidemic men and women before and after 9 to 12 months of exercise training. The training protocol resulted in significant changes in VO2max (mean +/- SD, +5.3 +/- 3.5 mL.kg-1 x min-1), body weight (-2.5 +/- 3.5 kg), plasma triglycerides (-25.7 +/- 36.3 mg/dL), high-density lipoprotein cholesterol (HDL-C) (+2.6 +/- 6.2 mg/dL), and ratios of total cholesterol to HDL-C (-0.30 +/- 0.52) and low-density lipoprotein cholesterol (LDL-C) to HDL-C (-0.18 +/- 0.45) (all P < or = .05) but no change in lipoprotein(a). CETP concentration (in milligrams per liter) fell significantly in response to training in both men (n = 28, 2.47 +/- 0.66 to 2.12 +/- 0.43; % delta = 14.2%; P < .005) and women (n = 29, 2.72 +/- 1.01 to 2.36 +/- 0.76; % delta = 13.2%; P < .047). The CETP change was observed both in subjects who lost weight (n = 28, delta mean weight = -5.0 kg; delta CETP = -0.42 +/- 0.79; % delta = 15.4%; P < .009) and in those who were weight stable (n = 29, delta mean weight = -0.12 kg; delta CETP = -0.29 +/- 0.78; % delta = 10.4%; P < .055).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗