Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determinations of lipoproteins (HDL-cholesterol and LDL-cholesterol) and various apolipoproteins (Apo A-I, Lp(a) and Apo B-100) were performed in postmortem pericardial fluid. Studies were carried out on 77 cadavers: 41 adult subjects with a morphological and biochemical diagnosis of intermediate or fresh myocardial infarction and 36 adults with no previous history of myocardial infarction. HDL and LDL were determined by enzymatic methods. Both apolipoproteins (A-I and B-100) were quantified by radio-immunoassay methods and Lp(a) was measured by enzyme immunoassay. Cases with severe atherosclerosis of coronary arteries showed higher levels of Apo B in pericardial fluid compared to cases without atherosclerosis. A significant increase of Apo B was found in cases with a positive diagnosis of myocardial infarction. Due to the high level of Apo B in pericardial fluid, a decrease in the LDL/Apo B ratio, along with a pronounced increase in the Apo B/Apo A ratio, was detected. The determination of Apo B in pericardial fluid can be a useful parameter to be included in biochemical analysis for the postmortem diagnosis of myocardial infarction related to coronary atherosclerosis.
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PMID:Lipoproteins and apolipoproteins in pericardial fluid: new postmortem markers for coronary atherosclerosis. 806 76

The plasma concentration of lipoprotein(a) (Lp(a)) is correlated with the risk of atherosclerosis, and both Lp(a) and LDL are present in atherosclerotic lesions. Lp(a) is similar in structure to LDL, its distinguishing feature from LDL being the presence of one additional glycoprotein, apo(a), that is linked to apoB-100. Upon incubation of 125I-LDL with isolated Lp(a), we found a dose and time-dependent increase in the proportion of TCA-soluble radioactive material, demonstrating degradation of LDL. The addition of unlabelled LDL decreased the degradation of 125I-LDL, while HDL or albumin had no such effect. Recombinant DNA-derived apo(a), R-apo(a), which itself expressed no amidolytic activity, displayed an increase in amidolytic activity after pre-incubation with LDL. Furthermore, activated R-apo(a) caused degradation of 125I-LDL. Treatment of R-apo(a) with phenylmethanesulfonyl fluoride inhibited LDL apoB-100 degradation, indicating that R-apo(a) has serine esterase type proteolytic activity. The results show that apo(a) is activated in the presence of LDL, and that this activation leads to proteolytic modification of LDL. The induction of apo(a) proteolytic activity by LDL suggests a novel mechanism whereby Lp(a) may be atherogenic.
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PMID:Proteolytic degradation of low-density lipoprotein by lipoprotein(a) and by recombinant apo(a). 818 21

Apolipoprotein B-100 (apo B-100) is the protein component of low density lipoprotein (LDL) responsible for its binding and clearance by LDL receptors (LDL-R). In familial defective apo B-100 (FDB), a mutation in apo B-100 at residue 3500 markedly reduces its affinity for LDL-R, often causing accumulation of defective LDL particles, and an increased proneness to coronary artery disease (CAD). In FDB heterozygotes, about 70% of the LDL particles are mutant, which may alter their atherogenicity relative to LDL containing normal apo B. Therefore, we compared CAD in heterozygous FDB with CAD in heterozygous familial hypercholesterolemia (FH), since raised LDL is usually present from birth in both conditions, and in FH the LDL particles that accumulate have normal apo B, as the inherited defect involves the LDL-R. The clinical presentation of coronary atherosclerosis and its angiographic appearance were examined in FDB and FH patients matched for conventional cardiac risk factors (hypertension, smoking, sex) and serum lipid levels. There was no significant difference between the FDB and FH patients (n=11 pairs) in the type of cardiac symptoms or their ages of onset (50 +/- 9 vs. 45 +/- 11 years). Coronary angiographic appearance was also similar in both groups (n=9 pairs). These observations suggest that LDL particles with the 3500 mutation in apo B have the same atherogenicity as LDL particles with normal apo B.
Atherosclerosis 1995 Nov
PMID:Does the presence of the 3500 mutant apolipoprotein B-100 in low density lipoprotein particles affect their atherogenicity? 857 20

The data described in this chapter demonstrate that the metabolic control of processes responsible for the formation, uptake and clearance of remnant particles is considerably more complex than previously believed. It now appears that several interacting reactions are involved in the process, and evidence is accumulating that defects in any one of these reactions may severely affect the optimal metabolic cascade. Proper exposure of receptor-binding domains in apoE and perhaps apoB-100 molecules is mandatory. Lipoprotein lipase-induced triglyceride hydrolysis is essential and responsible for the formation of remnant particles from secreted triglyceride-rich lipoproteins. The existence of apoE molecules that exhibit normal function is important but perhaps not always essential. Sequestration in the liver through lipoprotein lipase and/or apoE-mediated binding to heparan sulphate ('bridging' effect) appears to play an exceedingly important role during the early phase of the remnant clearance process. The 'bridging' is responsible not only for sequestration in the liver but also for enhanced uptake and lysosomal degradation of the particles. At this stage, association with the remnants of newly secreted, liver-derived apoE molecules may occur and add to the affinity of the particles towards receptors, especially if the new apoE molecules are inserted in a favourable conformational configuration. A role for the hepatic lipase has been suggested but is yet to be proved. Finally, it should be emphasized that remnants are cleared from the plasma predominantly, if not exclusively, following interaction with cellular receptors. Although the LDL receptor avidly internalizes remnant particles and is apparently active in species with a low LDL concentration (e.g. mice and rats), a second specialized and specific receptor or receptors must exist. Whether the LRP is the only remnant receptor or other, as yet unidentified, receptor proteins are also present, remains to be established. Data published in the last few years have begun to elucidate the interactions and consequences of the many reactions and proteins that are involved with the metabolism of remnant lipoproteins. More is to be learned, including the association of remnants in processes that lead to initiation/progression of atherosclerosis.
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PMID:Remnant particles and their metabolism. 859 23

It is well known that coronary heart disease (CHD) is multifactorial, with environmental and inherited risk factors both playing a role. Apolipoprotein B (apo B) is of major importance in lipoprotein metabolism and might play a central role in atherogenesis. The apo B gene is the obvious candidate gene to study the relations between lipid concentrations and CHD. Some rare mutations in the apo B gene affect plasma cholesterol levels, leading to either familial hypobetalipoproteinemia or familial defective apolipoprotein B100. Other frequent polymorphisms have little biological effect but, because of their high frequency, might contribute to the development of CHD in a given population. Many apo B gene polymorphisms are associated with variations in plasma lipid concentrations, including the response of plasma lipids to dietary intervention, and peripheral and coronary atherosclerosis. Age, body mass index and gender affect the degree and nature of the association between apo B genetic markers and normal lipid and lipoprotein levels. However, negative and contradictory results have also been reported. One likely explanation is differences between studies, including populations of different geographic origin, arbitrary definition of cases and controls and multiple criteria for CHD. Future work on the effect of the apo B locus on hyperlipidaemia and atherosclerosis must involve large numbers of patients belonging to carefully defined populations. Prospective studies using a combination of genetic markers in well-defined populations should lead to firm conclusions on the role of apo B in atherogenesis and coronary heart disease.
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PMID:[Genetic variation in the apolipoprotein B gene]. 862 6

The initial step in the process of atherosclerosis is supposed to be an increased penetration of lipoprotein particles (especially LDL or Lp(a)) into the subendothelial space. It occurs predominantly in regions with endothelial damage. After penetration into intima, LDL particles are oxidized. In endothelial cells, the incompletely oxidized LDL can induce expression of chemotactic factors which attract monocytes from circulation. Formation of adhesive molecules which enable immunocompetent cells to enter the subendothelial space can be simultaneously induced. As a response to stimulation induced by partially oxidized LDL, secretion of colony-forming factors is launched in endothelial cells. These factors induce monocyte to differentiate into macrophages. In subsequent oxidation, strongly oxidized LDL is formed. It is changed not only in the lipoid component but also in the structure of apolipoprotein B100 which brings about additional atherogenic properties. Another form of LDL particle modification is glycation. Absorption of large amounts of modified LDL particles by means of scavenger receptors or by phagocytosis of the lipoprotein complexes with antibody or proteoglycans, macrophages transform into foam cells which are typical for atherosclerotic lesions. In addition, activated macrophages secern various growth factors and cytokins stimulating vascular smooth muscle cells to migrate, proliferate and form extracellular matrix.
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PMID:[New findings on the pathogenesis of atherosclerosis]. 866 98

Genetic apo(a) isoforms were originally defined according to their relative mobility in SDS-PAGE compared to apoB-100 and were designated as F, B or S1-S4 isotypes. This widely accepted nomenclature does not accommodate the broad spectrum of apo(a) isoforms (> 30) detected by high resolution SDS-agarose gel electrophoresis. Moreover we here show that the relative mobilities of apo(a) isoforms depend on the SDS-gel system used. Comparison of the SDS-PAGE system originally used for phenotyping with SDS-agarose gel electrophoresis and two commercial SDS-PAGE systems (PhastGel, Pharmacia, Sweden and NOVEX, USA) demonstrated marked differences in resolving power and resulted in very different Rf values for identical isoforms. Hence phenotyping results from laboratories using different systems are not comparable. We therefore propose a nomenclature of apo(a) isoforms which reports the number of kringle IV repeats in the apo(a) allele (e.g. apo(a) K-IV20 would designate an isoform with 20 K-IV repeats). This is achieved by using standards in which the number of kringle IV repeats has been determined by pulsed field gel electrophoresis of genomic DNA. The proposed nomenclature (i) accounts for the increased resolution of apo(a) phenotyping methods: (ii) is flexible to the introduction of smaller or larger isoforms; (iii) allows to report data from systems with lower resolution as 'binned' isoform categories; (iv) allows the comparison of phenotyping results between different investigators; and (v) can be applied on DNA as well as on protein based apo(a) phenotyping.
Atherosclerosis 1996 Aug 23
PMID:The relative electrophoretic mobility of apo(a) isoforms depends on the gel system: proposal of a nomenclature for apo(a) phenotypes. 883 27

ApoA-II is a major apolipoprotein constituent of high density lipoproteins (HDL) and may play an important role in lipoprotein metabolism and predisposition to atherosclerosis. Previous radiotracer kinetic studies have suggested that the metabolism of apoA-II in humans may be different than the metabolism of apoA-I, the major HDL apolipoprotein. In the present study, we have used an endogenous labeling technique using stable isotopically labeled amino acids to study apoA-II metabolism and compared the results to those obtained by a simultaneous exogenous radiotracer labeling method. Seven subjects with HDL cholesterol levels ranging from 9 to 93 mg/dl and apoA-II levels from 13 to 60 mg/dl were investigated in this study. [13C6]phenylalanine and 131I-labeled apoA-II were simultaneously administered as a primed-constant infusion and a bolus injection, respectively. In the endogenous labeling study, plateau tracer/tracee ratios of VLDL apoB-100 were used as estimates for the precursor pool tracer/tracee ratios for apoA-II synthesis. Residence times of apoA-II using these two independent methods were found to be highly correlated (r = 0.973, P < 0.0002). These results indicate that the endogenous labeling of apoA-II using stable isotopically labeled amino acids is a reasonable alternative to the conventional exogenous radiotracer labeling method for the investigation of apoA-II turnover. However, under the conditions of our experimental design and modeling strategy, the apoA-II residence times as determined by endogenous labeling were significantly longer (mean 5.33 days) than by exogenous radiotracer (mean 4.65 days). This suggests that apoA-II turnover may be even slower than believed based on radiotracer studies, and further supports the concept that HDL containing apoA-II are metabolized differently than HDL without apoA-II.
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PMID:ApoA-II kinetics in humans using endogenous labeling with stable isotopes: slower turnover of apoA-II compared with the exogenous radiotracer method. 902 37

The plasma low density lipoprotein (LDL) of an apolipoprotein (apo) E-deficient patient was reported to contain apoB-48 (D. Kurosaka et al., Atherosclerosis 1988;88:15), which is a structural protein of chylomicrons and is not present in the fasting plasma LDL of normal subjects. We separated the LDLs containing apoB-48 (apoB-48 LDL) and apoB-100 (apoB-100 LDL) from the plasma of this patient using heparin-sepharose column chromatography. The apoB-48 LDL contained apoA-I, apoA-IV, and apoCs besides apoB-48. There were no differences in size and lipid composition of the apoB-48 and the apoB-100 LDLs, both of which contained more triglyceride than LDL from normal subjects. After incubation with apoE, the apoB-48 LDL contained twice the amount of apoE than the apoB-100 LDL and showed a marked decrease in apoA-I and apoA-IV content. These results suggest that lipoproteins containing apoB-48 in normal subjects can be quickly taken up through an apoE-mediated receptor mechanism after receiving apoE in exchange for apoA-I and A-IV.
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PMID:Purification and characterization of low density lipoprotein containing apolipoprotein B-48 from the plasma of an apoE-deficient patient. 908 98

Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles secreted from the liver accumulate in plasma during alimentary lipemia. To determine whether changes of VLDL composition occur in the postprandial state that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III, and lipids (triglycerides, phospholipids, and cholesterol) were measured in Svedberg flotation (Sf) 60-400 (large) and Sf 20-60 (small) VLDL before and after an oral fat load. Ten normotriglyceridemic (NTG) and three hypertriglyceridemic (HTG) healthy men were given a fat-rich mixed meal (1,000 kCal with 60.2 E% from fat). Triglyceride-rich lipoproteins were isolated by density gradient ultracentrifugation from plasma samples obtained before (fasting) and at 2-h intervals after the meal. VLDL was then separated from chylomicrons and their remnants by immunoaffinity chromatography using monoclonal antibodies 4G3 and 5E11, recognizing apoB-100, but not apoB-48 epitopes. Large and small VLDL isolated from the NTG group were enriched with apoE and C-I, and cholesterol, but depleted of apoC-II in the postprandial state, whereas the apoC-III, triglyceride, and phospholipid contents were essentially unchanged. The compositional changes of VLDL in HTG subjects were similar but more pronounced compared with NTG subjects. We conclude that postprandial lipemia in healthy men induces transient compositional alterations of VLDL that link these lipoprotein species to the formation of atherosclerosis.
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PMID:Alterations of VLDL composition during alimentary lipemia. 916 50


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