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)

Triglyceride-rich lipoprotein (TRL) remnants are formed in the circulation when apolipoprotein (apo) B-48-containing chylomicrons of intestinal origin or apoB-100-containing VLDL of hepatic origin are converted by lipoprotein lipase, and to a lesser extent by hepatic lipase, into smaller and more dense particles. Compared with their nascent precursors, TRL remnants are depleted of triglyceride, phospholipid, and C apolipoproteins and are enriched in cholesteryl esters and apoE. They can thus be identified, separated, and/or quantified in plasma according to their density, charge, size, specific lipid components, apolipoprotein composition, and/or apolipoprotein immunospecificity. Each of these approaches has contributed to our current understanding of the compositional characteristics of TRL remnants and their potential to promote atherosclerosis. An ongoing search is nevertheless under way for more accurate and clinically applicable remnant lipoprotein assays that will be able to better define coronary artery disease risk in patients with hypertriglyceridemia.
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PMID:Detection, quantification, and characterization of potentially atherogenic triglyceride-rich remnant lipoproteins. 1052 78

A recent study has suggested that symptoms of chronic bronchitis predict the risk of coronary disease independently of the known major cardiovascular risk factors. High serum levels of lipoprotein(a) (Lp(a)) have also been considered as an independent risk factor for coronary heart disease. Therefore, the aim of the present study was to investigate the behaviour of Lp(a) in patients affected by chronic obstructive pulmonary disease (COPD). Serum levels of total-cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, apolipoprotein (Apo) B-100, and Lp(a) were measured in 90 COPD patients and in 90 normal subjects matched for age, sex and smoking habit. COPD patients showed lower serum levels of Apo B-100 (P<0.0001) and Lp(a) (P<0.003) compared to controls. Conversely, TC, HDL-C, LDL-C and triglycerides were similar between patients and controls. No significant differences were found in Apo B-100 and Lp(a) levels of patients either undergoing different therapeutic regimens, or with different smoking habits. A significant correlation between Apo B-100 and Lp(a) (rho=0.433, P<0. 0001) was also observed. In conclusion, COPD patients do not show an atherogenetic lipid pattern and their increased risk of coronary disease could be attributable to different factors, such as the ongoing hypercoagulability state often associated with COPD.
Atherosclerosis 1999 Dec
PMID:Lipoprotein(a) serum levels in patients affected by chronic obstructive pulmonary disease. 1134 Dec 34

It is suggested that intracellular deficiency of polyenic fatty acids (FA) is the biochemical basis of atherosclerosis. Its cause in the presence of abundant blood polyenic FA as cholesterol esters (cholesterol-esterified polyenic FA) is blockade of apoB-100-receptor endocytosis. The occurrence of polyenic FA deficiency in phylo- and ontogenesis and the cell adaptation reactions which accomplish the cell transfer and receptor absorption of polyenic FA are considered. The pathogenesis of atherosclerosis is a long-term adaptation to deficient cellular essential FA. At the same time the cells form a plasma membrane, synthesize thromboxanes, prostaglandins, and leukotrienes from omega-9-dihomo-Y-linolenic FA rather than from essential omega-6-arachidonic and omega-3-eicosapentaenic acids. This adaptation process determines all metabolic disturbances which are peculiar to atherosclerosis.
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PMID:[Atherosclerosis as a problem of general biology: cell adaptation to deficiency of essential fatty acids]. 1057 66

Elevated low density lipoprotein cholesterol (LDL-C) and reduced high density lipoprotein cholesterol (HDL-C) concentrations are independent risk factors for coronary heart disease. We have previously demonstrated that overexpression of an enzyme with a well established role in HDL metabolism, lecithin:cholesterol acyltransferase (LCAT), in New Zealand White rabbits not only raises HDL-C concentrations but reduces those of LDL-C as well, ultimately preventing diet-induced atherosclerosis. In the present study, the human LCAT gene (hLCAT) was introduced into LDL receptor (LDLr)-deficient (Watanabe heritable hyperlipidemic) rabbits to (1) investigate the role of the LDLr pathway in the hLCAT-mediated reductions of LDL-C and (2) determine the influence of hLCAT overexpression on atherosclerosis susceptibility in an animal model of familial hypercholesterolemia. Heterozygosity or homozygosity for the LDLr defect was determined by polymerase chain reaction, and 3 groups of hLCAT-transgenic (hLCAT+) rabbits that differed in LDLr status were established: (1) LDLr wild-type (LDLr+/+), (2) LDLr heterozygotes (LDLr+/-), and (3) LDLr homozygotes (LDLr-/-). Data for hLCAT+ rabbits were compared with those of nontransgenic (hLCAT-) rabbits of the same LDLr status. Plasma HDL-C concentrations were significantly elevated in the hLCAT+ animals of each LDLr status. However, LDL-C levels were significantly reduced only in hLCAT+/LDLr+/+ and hLCAT+/LDLr+/- rabbits but not in hLCAT+/LDLr-/- rabbits (405+/-14 versus 392+/-31 mg/dL). Metabolic studies revealed that the fractional catabolic rate (FCR, d(-1)) of LDL apolipoprotein (apo) B-100 was increased in hLCAT+/LDLr+/+ (26+/-4 versus 5+/-0) and hLCAT+/LDLr+/- (4+/-1 versus 1+/-0) rabbits, whereas the FCR of LDL apoB-100 in both groups of LDLr-/- rabbits was nearly identical (0.16+/-0.02 versus 0.15+/-0.02). Consistently, neither aortic lipid concentrations nor the extent of aortic atherosclerosis was significantly different between hLCAT+/LDLr-/- and hLCAT-/LDLr-/- rabbits. Significant correlations were observed between the percent of aortic atherosclerosis and both LDL-C (r=0.985) and LDL apoB-100 FCR (-0.745), as well as between LDL-C and LDL apoB-100 FCR (-0.866). These data are the first to establish that LCAT modulates LDL metabolism via the LDLr pathway, ultimately influencing atherosclerosis susceptibility. Moreover, LCAT's antiatherogenic effect requires only a single functional LDLr allele, identifying LCAT as an attractive gene therapy candidate for the majority of dyslipoproteinemic patients.
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PMID:LCAT modulates atherogenic plasma lipoproteins and the extent of atherosclerosis only in the presence of normal LDL receptors in transgenic rabbits. 1066 43

Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.
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PMID:[Familial hypercholesterolemia]. 1068 42

Apolipoprotein B-100 (apo B-100) plays an essential role in lipoprotein metabolism where it is involved in the clearance of LDL particles from the bloodstream. The mutation Arg3500Gln in the apo B-100 gene impairs the binding of the LDL particles to the LDL receptor, resulting in elevated LDL-cholesterol levels in the blood which, in turn, fuel the development of premature atherosclerosis. Here we describe a rapid, automated test for the detection of the most frequent mutation in the apo B-100 gene. This PCR-based test employs electrochemiluminescence as detection technology and allows the reliable discrimination of all genotypes. The assay has been especially developed for the non-specialized routine clinical chemistry laboratory by employing an analyzer and chemistry often present in this type of labof1tory. Because of its low costs and easy handling the assay can be performed on a daily basis.
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PMID:Apolipoprotein B-100: employing the electrochemiluminescence technology of the Elecsys systems for the detection of the point mutation Arg(3500)Gln. 1074 80

The aim of the present cross-sectional angiographic study was to examine if there is a relationship between the severity of CAD and postprandial lipemia in patients with type 2 diabetes mellitus. Special emphasis was directed to determining the contribution of apolipoprotein B-48 (apoB-48)-containing and B-100 (apoB-100)-containing triglyceride-rich particles to the magnitude of postprandial lipemia and degree of CAD. The role of apolipoprotein E (apoE) phenotype as a modulator of postprandial lipemia was also evaluated. The severity of CAD was determined by a quantitative coronary angiography and the subjects were classified into two groups based on the presence (severe CAD) or absence (mild CAD) of at least 50% stenosis in a major coronary vessel. The study population consisted of 43 subjects (31 men and 12 women) with fair glycemic control and comparable fasting lipids and body mass index. Postprandial responses of TG, apoB-48 and apoB-100 in lipoprotein subfractions (chylomicrons, VLDL1, VLDL2 and IDL) were determined after a fat load. Type 2 diabetic patients exhibited the classical dyslipidemia of the insulin resistance syndrome and delayed clearance of both hepatic and intestinal particles. Fasting or postprandial lipid or lipoprotein measurements, including apoB-48 and apoB-100 concentrations, did not differ between the groups. The presence or absence of apoE-4 allele did not significantly influence postprandial lipemia. The severity of the most significant coronary stenosis in angiography correlated with plasma and with chylomicron area under curve (AUC) for TG (n=27) and chylomicron AUC for apoB-48 (n=20). The strongest correlate of maximal stenosis was area under incremental curve (AUIC) for apoB-100 in IDL fraction (r=0.548, P=0. 012, n=20). In conclusion, postprandial apoB-48 and apoB-100 metabolism in triglyceride rich lipoproteins is distorted in type 2 diabetic patients, even in those with only mild CAD. The data suggest that postprandial change in small remnant particle numbers may contribute to the severity of CAD in type 2 diabetes.
Atherosclerosis 2000 May
PMID:Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease. 1078 48

We investigated the effect of nephropathy on the composition of apolipoprotein-containing particles in non-obese NIDDM patients with normocholesterolemia. Sixty-seven normal control subjects (group A), 48 NIDDM patients without nephropathy (group B) and 36 NIDDM patients with nephropathy (group C) were studied. Apolipoprotein AI or B100 containing particles (Apo AI or Apo B100) were isolated by immunoaffinity columns prepared with monoclonal antibodies. The total cholesterol (CH), esterified cholesterol (EC) and free cholesterol (FC) content in these particles was analyzed. Both the EC/FC ratio levels in Apo AI and in Apo B100 in group C were significantly higher than those in group A or B. Both the CH in Apo AI/apolipoprotein AI ratio and in Apo B100/apolipoprotein B100 ratio levels in group C were significantly lower than those in group A or B. The insulin resistance index showed significant positive correlation with the EC/FC ratio levels in Apo AI and in Apo B100, and showed significant negative correlation with the CH levels in Apo AI/apolipoprotein AI ratio and the CH levels in Apo B100/apolipoprotein B100 ratio levels in group C. Those compositional changes of lipoproteins in NIDDM patients with nephropathy may reflect partial insulin resistance and deteriorating atherosclerosis.
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PMID:Effect of nephropathy on the composition of apolipoprotein-containing particles in NIDDM. 1085 58

Atherosclerosis is the leading cause of death in North America. It is characterized by thickening of the coronary artery wall by the formation of plaques, resulting in reduced blood flow. Plaque rupture and the consequent thrombosis may lead to sudden blockage of arteries and causing stroke and heart attack. In the last several decades, more than 250 factors associated with the development of coronary artery disease have been identified. Recently, a relationship between atherosclerosis and elevated homocysteine level in the blood has been established. The mechanism for the production of atherosclerosis by homocysteine has been investigated. When human hepatoma cells (HepG2) were incubated with 4 mM homocysteine, enhancements in the production of cholesterol and secretion of apolipoprotein B-100 were observed. The stimulatory effect on cholesterol synthesis was mediated via the enhancement of HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol biosynthesis. Cholesterol appears to play an important role in the regulation of apoB-100 secretion by hepatocytes. It is plausible that the increase in apoB secretion was caused by the elevated cholesterol level induced by homocysteine. The ability of homocysteine to produce a higher amount of cholesterol and promote the secretion of apoB would provide a plausible mechanism for the observed relationship between hyperhomocysteinemia and the development of atherogenesis and coronary artery disease.
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PMID:Atherosclerosis risk factors: the possible role of homocysteine. 1088 40

This study was conducted to investigate the influence of dietary zinc on intestinal apoB mRNA editing in hamsters. Apolipoprotein B-48 (apoB-48) is synthesized from the same gene as apoB-100 by a post-transcriptional, site-specific cytidine deamination, a process known as apoB mRNA editing. A cDNA encoding the hamster apoB mRNA editing enzyme was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) and the deduced amino acid sequence was found to possess high amino acid sequence identity to apoB mRNA editing enzymes from several other species. Editing activity was detected in the small intestine and colon but, like humans, none was detected in the liver. Analysis by RT-PCR indicated that the small intestine possessed the highest expression of editing enzyme mRNA abundance, whereas both liver and small intestine expressed relatively high levels of apoB mRNA. The influence of dietary zinc on intestinal apoB mRNA editing levels was examined in Golden Syrian hamsters (7 wk old) assigned to one of the following three dietary treatments: Zn-adequate (ZA, 30 mg Zn/kg diet), Zn-deficient (ZD, <0. 5 mg Zn/kg diet), or Zn-replenished (ZDA, ZD hamsters receiving ZA diet for last 2 d) for 7 wk. Hamsters consuming the ZD diet had modestly but significantly lower intestinal editing activity than ZA hamsters. Intestinal editing activity in the ZDA group was not different from that of ZA hamsters. Data derived from these studies contribute to the understanding of lipoprotein metabolism in hamsters, a suitable model for the study of atherosclerosis.
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PMID:Regulation of intestinal apolipoprotein B mRNA editing levels by a zinc-deficient diet and cDNA cloning of editing protein in hamsters. 1095 8


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