Journal ArticleDOI
Occurrence of species of low-density lipoprotein with defective clearance in patients with primary moderate hypercholesterolaemia
Gloria Lena Vega,Scott M. Grundy +1 more
Reads0
Chats0
TLDR
A significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation, suggesting that two forms of LDL might be separable by ultracentrifugation.Abstract:
Recent studies have shown that one cause of primary moderate hypercholesterolaemia is familial defective apolipoprotein B-100 (FDB), a condition in which a mutation in apolipoprotein B-100 (apo B-100) causes low-density lipoproteins (LDL) to bind poorly to LDL receptors. One specific mutation, a glutamine-for-arginine transformation at position 3500 of apo B-100, has been reported to produce FDB. However, other mutations in apo B-100 might also cause FDB. The present study was designed to determine whether some patients with hypercholesterolaemia, who do not have the 3500 defect, may have a slowly cleared subfraction of LDL compatible with other forms of FDB. It was postulated that slowly removed LDL should accumulate excess cholesterol ester and hence be less dense than normal LDL. If so, in patients who are heterozygous for FDB, two forms of LDL might be separable by ultracentrifugation. To test this hypothesis, less-dense (d = 1.030 g ml-1) and more-dense (d = 1.040 g ml-1) subfractions of LDL were isolated from a patient with proven FDB (3500 mutation); the two forms of LDL were labelled with different isotopes of radioiodine and re-injected into the patient. The less-dense form was removed much more slowly (0.285 pools day-1) than more-dense LDL (0.570 pools day-1). This finding appeared to confirm the validity of the approach. The same procedure was then applied to 18 other patients having elevated LDL cholesterol but not the 3500 mutation. In 13 patients, the two forms of LDL were removed at essentially identical rates, suggesting that they did not have an abnormal form of LDL. In the other five, less-dense LDL were removed at a significantly slower rate than more-dense LDL; this finding suggests that a significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation.read more
Citations
More filters
Journal ArticleDOI
The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.
Jean-Charles Fruchart,Frank M. Sacks,Michel P. Hermans,Gerd Assmann,W. Virgil Brown,Richard Ceska,M. John Chapman,Paul M. Dodson,Paola Fioretto,Henry N. Ginsberg,Takashi Kadowaki,Jean-Marc Lablanche,Nikolaus Marx,Jorge Plutzky,Zeljko Reiner,Robert S. Rosenson,Bart Staels,Jane K Stock,Rody G. Sy,Christoph Wanner,Alberto Zambon,Paul Zimmet +21 more
TL;DR: Evidence is highlighted that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care, and therapeutic intervention is recommended for reducing this residual vascular risk supported by evidence and expert consensus.
Journal ArticleDOI
Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment.
Helena Gylling,Tatu A. Miettinen +1 more
TL;DR: It is concluded that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased.
Journal ArticleDOI
Role of low-density lipoproteins in atherogenesis and development of coronary heart disease.
TL;DR: There is a strong association between increased blood concentrations of low-density lipoprotein (LDL) and severity of coronary atherosclerosis, and current concepts of LDL metabolism are extensively reviewed.
Journal ArticleDOI
Mutation screening of the codon 3500 region of the apolipoprotein B gene by denaturing gradient-gel electrophoresis.
TL;DR: The DGGE method both detects known FDB mutations and screens for other mutations in codons 3456-3553 of the low-density lipoprotein receptor binding region of apo B-100; it can be used as a first-line screening method for FDB.
Journal ArticleDOI
Simultaneous measurements of chylomicron lipolysis and remnant removal using a doubly labeled artificial lipid emulsion: studies in normolipidemic and hyperlipidemic subjects.
Edna Regina Nakandakare,Simão Augusto Lottenberg,Helena C. F. Oliveira,M. C. Bertolami,K. S. Vasconcelos,Giuseppe Sperotto,Eder Carlos da Rocha Quintão +6 more
TL;DR: An artificial chylomicron-like lipid emulsion doubly labeled with tri[(N)3H]oleoylglycerol and cholesteryl [1-14C]oleate was infused intravenously into human subjects with the purpose of simultaneously measuring the plasma disappearance rates.
References
More filters
Journal Article
Protein Measurement with the Folin Phenol Reagent
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
Journal ArticleDOI
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
Scott M. Grundy,David W. Bilheimer,Alan Chait,Luther T. Clark,Margo A. Denke,Richard J. Havel,William R. Hazzard,Stephen B. Hulley,Donald B. Hunninghake,Robert A. Kreisberg,Penny M. Kris-Etherton,James M. McKenney,Michael A. Newman,Ernst J. Schaefer,Burton E. Sobel,Carolyn Somelofski,Milton C. Weinstein,H. Bryan Brewer,James I. Cleeman,Karen A. Donato,Nancy D. Ernst,Jeffrey M. Hoeg,Basil M. Rifkind,Jacques E. Rossouw,Christopher T. Sempos,Joanne M. Gallivan,Maureen N. Harris,Laurie Quint-Adler +27 more
TL;DR: Dairy therapy remains the first line of treatment of high blood cholesterol, and drug therapy is reserved for patients who are considered to be at high risk for CHD, and the fundamental approach to treatment is comparable.
Journal ArticleDOI
A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples
TL;DR: The original Lowry method of protein determination has been modified by the addition of sodium dodecyl sulfate in the alkali reagent and an increase in the amount of copper tartrate reagent to be used with membrane and lipoprotein preparations without prior solubilization or lipid extraction.
Journal ArticleDOI
A receptor-mediated pathway for cholesterol homeostasis.
TL;DR: The approach was to apply the techniques of cell culture to unravel the postulated regulatory defect in FH, which led to the discovery of a cell surface receptor for a plasma cholesterol transport protein called low density lipoprotein (LDL) and to the elucidation of the mechanism by which this receptor mediates feedback control of cholesterol synthesis.
Journal ArticleDOI
Efficient trace-labelling of proteins with iodine.
TL;DR: Values greater than 50 per cent can be obtained by adding oxidizing agents to liberate iodine from iodide, but most if not all of these appear to affect adversely the properties of the labelled protein.