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)

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

One hundred and fifty-four male and 69 female Chinese patients, aged between 40 and 60 years, who had suffered myocardial infarction (MI) were investigated and compared with 216 men and 219 women who had no history or ECG evidence of coronary heart disease. The male MI patients had significantly raised levels of triglycerides (160 mg/dl), cholesterol (194 mg/dl), VLDL-CH (31 mg/dl), apolipoprotein B (122 mg/dl) and apolipoprotein E (4.7 mg/dl) and a lower apolipoprotein A-I level (126 mg/dl) than the control group (triglycerides 131, cholesterol 179, VLDL-CH 26, apo B 102, apo E4.2, and apo A-I 138 mg/dl). The women with MI also had higher values for the atherogenic lipids than the control group (triglycerides 175 vs. 134 mg/dl, cholesterol 218 vs. 186 mg/dl, LDL-CH 128 vs. 104 mg/dl, VLDL-CH 32 vs. 26 mg/dl, apo B 121 vs. 103 mg/dl and apo E 5.4 vs. 4.3 mg/dl), as well as lowered apolipoprotein A-I (128 vs. 144 mg/dl). The Lp(a) levels (men and women considered together) were significantly higher for the MI patients (34.3 mg/dl vs. 26.2 mg/dl). Anti-atherogenic lipoproteins such as HDL-cholesterol, HDL2-CH, HDL3-CH, phospholipids and apolipoprotein A-II, C-II and C-III showed no difference between the groups.
Atherosclerosis 1990 Jun
PMID:Lipids, lipoproteins, apolipoproteins, and other risk factors in Chinese men and women with and without myocardial infarction. 237 89

Methylated DNA-binding protein (MDBP), a sequence-specific DNA-binding protein, was found to recognize more than 30 sites within an allele of the human apolipoprotein(a) gene. High plasma levels of apolipoprotein(a), a risk factor for atherosclerosis, have been correlated with genetically inherited lower-molecular-mass isoforms of this protein. MDBP might help down modulate the expression of the apolipoprotein(a) gene in a manner dependent on the length of a given allele of the gene and the number of MDBP sites in it.
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PMID:Highly repeated sites in the apolipoprotein(a) gene recognized by methylated DNA-binding protein, a sequence-specific DNA-binding protein. 238 31

Lipoprotein (a) is believed to be an independent risk factor for atherosclerosis. Fat modified diets or lipid lowering drugs seem to have little effect on Lp(a) serum levels. We tested the possibility of lowering Lp(a) by weight reduction and examined the correlation between Lp(a) serum levels, other lipoproteins, body weight and body fat distribution in 53 obese patients. Weight reduction by a 4000 kJ protein enriched diet for four weeks led to a mean 19 percent reduction of Lp(a) serum levels in men (P less than 0.01) and a mean 30 percent reduction in premenopausal women (P less than 0.001). Significant correlations could neither be demonstrated between Lp(a) and other lipoproteins nor between initial Lp(a), overweight and body fat distribution. This implies that an intraindividual interdependence between Lp(a) and body weight seems to be possible although an interindividual correlation can not be shown.
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PMID:Reduction of lipoprotein (a) by weight loss. 240 85

Serum lipoprotein(a) (Lp(a)) was serially determined after acute attacks of myocardial infarction and after surgical operations. Acute phase proteins, such as C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antitrypsin and haptoglobin, increased rapidly and markedly after the episodes. Initial values of serum Lp(a) concentrations were almost the same in both groups. Increases in serum Lp(a) levels were also observed during the first few days, with a return to the initial levels after more than 1 month. The periods for reaching maximal levels of acute phase proteins were similar in both groups of patients. On the contrary, the period required for Lp(a) to reach the maximal level in the myocardial infarction group was significantly longer than in the post-operative group. The present study suggests that Lp(a) has the characteristics of an acute phase reactant and may play an important role in recovery from tissue damage.
Atherosclerosis 1989 Aug
PMID:Transient changes of serum lipoprotein(a) as an acute phase protein. 247 92

The contribution of genes to the etiology of coronary heart disease (CHD) is highly significant even when monogenic hyperlipidemias are excluded. Previous studies in the area of quantitative genetics and of disease or risk factor association with random genetic markers have, in recent years, been supplemented with studies focused on "candidate genes"--genes whose products are known or suspected to be involved in the atherogenic process, the thrombogenic process, lipid metabolism, or apolipoprotein (apo) structure or function. In 1974, the candidate gene approach led to the detection of a strong association between genetically determined Lp(a) lipoprotein and premature CHD and, in 1976, also led to the detection, in several populations, of the association between lipid levels and genetic types in the normal low density lipoprotein (LDL) polymorphism referred to as the Ag(x) variation. Restriction fragment length polymorphisms in DNA have been uncovered in the genes for several functionally important proteins including apos. Some of these DNA variants have been reported to be associated with CHD or lipid level. Such variants should become useful tools in predictive genetic testing for CHD risk. Most studies on the genetics of risk factors have focused on risk factor level. Because an individual's propensity to develop atherosclerosis could depend not only on absolute lipid levels but also on lipid responses to atherogenic stimuli, we have developed a method to examine if "variability genes" exist. To detect the latter class of genes, we examine within-pair differences in quantitative parameters between monozygotic (MZ) twin pairs possessing and MZ twin pairs lacking the gene under study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predictive genetic testing to control coronary heart disease and hyperlipidemia. 252 45

Endothelial cells play a critical role in thromboregulation by virtue of a surface-connected fibrinolytic system. Cultured endothelial cells synthesize and secrete tissue-type plasminogen activator (t-PA) which can bind to at least two discrete sites on the cell surface. These binding sites preserve the catalytic activity of t-PA and protect it from its physiological inhibitor (PAI-1). N-terminal glutamic acid plasminogen (Glu-PLG), the main circulating fibrinolytic zymogen, also interacts specifically with the endothelial cell surface. Binding is associated with a 12-fold increase in catalytic efficiency of plasmin generation by t-PA which may reflect conversion of Glu-PLG to its plasmin-modified form, N-terminal lysine plasminogen (Lys-PLG). Lipoprotein(a) is an atherogenic lipoprotein particle which contains the plasminogen-like apolipoprotein(a) bound to low density lipoprotein. We report here that lipoprotein(a) interferes with endothelial cell fibrinolysis by inhibiting plasminogen binding and hence plasmin generation. In addition, we demonstrate lipoprotein(a) accumulation in atherosclerotic lesions. These findings may provide a link between impaired cell surface fibrinolysis and progressive atherosclerosis.
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PMID:Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. 252 66

Lipoprotein (a) [Lp(a)] is a plasma component whose concentration is related to the development of atherosclerosis, although the underlying mechanisms are not known. Lp(a) contains a unique structure, apolipoprotein (a), that shares partial homology with plasminogen. We now report that plasmin catalyzes the binding of Lp(a) to both immobilized fibrinogen and fibrin in a manner analogous to our previously reported studies with plasminogen. Plasmin treatment of immobilized fibrinogen induces a 3.7-fold increase in Lp(a) binding. Low density lipoprotein, molecules similar to Lp(a) but lacking apolipoprotein (a), bind poorly to immobilized fibrinogen and binding is not increased by plasmin. Trypsin but not neutrophil elastase also increases the binding of Lp(a) to fibrinogen. Lp(a) also complexes to plasmin-fibrinogen digests, and binding increases in proportion to the time of plasmin-induced fibrinogen degradation. Lp(a) binding is lysine-binding site dependent as it is inhibited by epsilon-aminocaproic acid. Lp(a) inhibits the binding of plasminogen to plasmin-modified immobilized fibrinogen, indicating that both molecules compete for similar lysine-binding sites. These findings demonstrate an affinity between Lp(a) and protease-modified fibrinogen or fibrin and thereby provide a potential mechanism to explain the association between thrombosis, coronary atherosclerosis, and increased blood concentrations of Lp(a).
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PMID:Plasmin catalyzes binding of lipoprotein (a) to immobilized fibrinogen and fibrin. 252 34

Lipoprotein(a) (Lp(a] immunoreactive materials were examined in serum samples from 77 nonhuman primates of 24 species by Ouchterlony's double diffusion procedure and an enzyme-linked immunosorbent assay (ELISA) using rabbit antisera to human Lp(a). The precipitates obtained with sera from orang-utan and chimpanzee formed reactions of complete identity with the Lp(a) precipitate with human serum. When sera from Old World monkeys and human subjects were tested in wells next to each other, spurs developed between the 2 precipitates, indicating that Lp(a)-like lipoproteins in Old World monkeys have partial identity with human Lp(a). Lp(a) immunoreactive materials were identified in association with lipids by means of fat staining of the precipitates. On the other hand, reactants which could be precipitated with anti-human Lp(a) sera were not detectable in prosimians and New World monkeys. These results suggest that serum Lp(a)-like lipoprotein is phylogenetically acquired in Old World monkeys. However, the possibility that the structures of serum Lp(a)-like lipoproteins in prosimians and New World monkeys are too different to react with anti-human Lp(a) sera cannot be ruled out.
Atherosclerosis 1989 Jul
PMID:Lipoprotein(a) in nonhuman primates. Presence and characteristics of Lp(a) immunoreactive materials using anti-human Lp(a) serum. 252 36

This new, sensitive, specific "sandwich"-type enzyme-linked immunosorbent assay (ELISA) for quantifying lipoprotein(a) [Lp(a)] in human serum and in ultracentrifugal lipoprotein fractions is based on use of a monoclonal antibody raised against apolipoprotein(a) as coating protein and a polyclonal antibody, raised against either apo B or against Lp(a) and conjugated with peroxidase, for detection of bound Lp(a). Mean intra- and interassay CVs for assay of 16 samples were 3.0% and 5.6%, respectively. Sample pretreatment with urea did not enhance Lp(a) immunoreactivity, and treatment with nonionic detergents decreased binding to the monoclonal antibody. Results correlated well (r = 0.99, n = 38) with those by radial immunodiffusion (RID). The ELISA assay, however, detects amounts corresponding to Lp(a) contents of 10 to 1000 mg/L in plasma samples diluted 1000-fold, compared with 100-500 mg/L for RID. For 92 normolipidemic subjects, the mean Lp(a) concentration was 120 (SD 130) mg/L. In patients undergoing coronary angiography, Lp(a) concentrations increased with the severity of the disease but were not correlated with either HDL cholesterol, triglycerides, apo A-I, or apo B, and only weakly with plasma cholesterol and apo A-II. These two correlations were even weaker in normal subjects, and only the correlation with total cholesterol was valid. Lp(a), measured at birth and at seven days and six months, steadily increased with age. This assay is well suited for measuring Lp(a) in plasma and in lipoprotein fractions and also for screening programs evaluating this significant genetic risk factor for the development of atherosclerosis.
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PMID:Lipoprotein(a) quantified by an enzyme-linked immunosorbent assay with monoclonal antibodies. 252 93


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