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)

Some important enzymes concerned with the biosynthesis of the precursors of glycosaminoglycans (gg), degradation of gg and biological sulphation have been studied in rats fed an atherogenic diet. L-Glutamine-D-fructose-6-phosphate amino-transferase and glucosamine-6-phosphate-N-acetylase--2 enzymes concerned with the biosynthesis of hexosamine precursors of gg--decreased in the liver in rats fed the atherogenic diet. UDPG pyrophosphorylase, UDPG dehydrogenase and UDPG glucuronic acid-5'-epimerase, which are concerned with the biosynthesis of the uronic precursors of gg, also decreased in the liver in the diet-fed rats. The activities of some of the enzymes concerned with degradation of gg-hyaluronidase, beta-glucuronidase beta-hexosaminidase, cathepsin and aryl sulphatase--increased both in the liver and aorta. The hepatic concentration of PAPS significantly decreased in the diet-fed rats. The sulphate-activating system, which includes ATP sulphurylase, APS kinase and sulphotransferase, also decreased. Thus the overall picture is one of decreased synthesis of gg and their increased degradation in the atheromatous rats.
Atherosclerosis
PMID:Metabolism of glycosaminoglycans in atheromatous rats. Enzymes concerned with synthesis, degradation and sulphation of glycosaminoglycans. 12 76

The effect of low and high doses of ascorbic acid on glycosaminoglycan and lipid metabolism was studied in guinea pigs fed both normal and atherogenic diets. The high dose of ascorbic acid (25 mg/100 g body weight/day) decreased the cholesterol level in the liver and aorta but not in the serum in animals fed the normal diet in comparison with those fed the low dose of ascorbic acid (0.1 mg/100 g body weight/day). In animals fed the atherogenic diet, cholesterol decreased in the serum and liver, but not in the aorta. Serum triglycerides were not affected by the dose of ascorbic acid in the group on the normal diet, but in the animals receiving the atherogenic diet, the high dose of ascorbic acid caused serum triglycerides to decrease when compared with the low dose. Hepatic and aortic triglycerides decreased in groups on normal and atherogenic diets receiving the high dose of ascorbic acid. Lipoprotein lipase activity was not affected in the aorta by the dose of ascorbic acid either in the normal or atherogenic diet group. It was increased in the liver and heart in both the groups receiving the low dose of ascorbic acid but decreased in the high dose group. The concentration of all the glycosaminoglycans significantly increased in the aorta of animals on normal diet receiving the high dose of ascorbic acid when compared with the low dose group. In the group on the atherogenic diet, hyaluronic acid was not affected, but all the sulphated glycosaminoglycans increased in the animals receiving the high dose when compared with those receiving the low dose. In the liver all the sulphated glycosaminoglycans increased while hyaluronic acid decreased in both the normal and atherogenic diet groups receiving the high rather than the low dose of ascorbic acid. L-Glutamine:D-fructose-6-phosphate aminotransferase and UDPG dehydrogenase, two key enzymes in the biosynthesis of precursors of glycosaminoglycans, were studied in relation to the dose of ascorbic acid. Hepatic aminotransferase activity was higher both in the normal and atherogenic diet groups when receiving the high rather than the low dose of ascorbic acid. UDPG dehydrogenase was not affected by the dose of ascorbic acid. The activities of the degrading enzymes -- hyaluronidase, beta-glucuronidase, beta-hexosaminidase and aryl sulphatase -- significantly increased both in the normal and atherogenic diet groups when receiving the low rather than the high dose of ascorbic acid. The concentration of PAPS, sulphate activity and sulphotransferase activity were all increased in both the normal and atherogenic diet groups receiving the high dose of ascorbic acid.
Atherosclerosis
PMID:Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets. 12 67

The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2-week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL.
Atherosclerosis 1992 Aug
PMID:Effective reduction of plasma LDL levels by LDL apheresis in familial defective apolipoprotein B-100. 141 96

Familial defective apolipoprotein B-100 is a recently identified, dominantly inherited genetic disorder caused by a G to A mutation in exon 26 of the apolipoprotein B gene. This creates a substitution of glutamine for arginine in the codon for amino acid 3500 and results in reduced affinity of low density lipoprotein (LDL) to the LDL receptor. We have integrated already published data with hitherto unpublished data from 8 countries and a total of 135 affected individuals from 56 families, in an attempt to focus on the range of expression of this mutation on lipid and lipoprotein levels and on coronary artery disease. The frequency of this mutation may be as high as 1 in 500 to 1 in 700 in Europe and in North America. The vast majority of affected heterozygotes have total and LDL cholesterol levels well above the 95th centile for age and gender; in contrast, high density lipoprotein cholesterol, very low density lipoprotein cholesterol and plasma triglycerides are not affected by the mutation. The risk of premature coronary artery disease in the carriers of the mutation is increased to levels as high as those seen in patients with clinical familial hypercholesterolemia; at age 50, about 40% of males and 20% of females heterozygous for the mutation have developed coronary artery disease. Familial defective apolipoprotein B-100 is thus a significant cause of hypercholesterolemia and premature coronary artery disease in Western societies.
Atherosclerosis 1992 Oct
PMID:Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease. 146 57

Forty-three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B-100 arginine3500-->glutamine mutation. This receptor-binding defective apolipoprotein B variant is the cause of familial defective apo B-100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP.
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PMID:Screening for the apolipoprotein B-100 arginine3500-->glutamine mutation in patients with type III hyperlipoproteinemia. 149 42

Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine (3500)----glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine(3500)----glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine(3500)----glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to "classic" familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor-defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100.
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PMID:Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia. 160 Mar 34

Familial defective apolipoprotein B100 (FDB) is a recently identified dominantly inherited genetic disorder, which is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor. FDB is caused by a G to A mutation at nucleotide 10 708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To determine the consequences of the arginine(3500)----glutamine mutation on plasma lipid levels and other clinical features, we have investigated 54 FDB heterozygotes from Germany (24 men, 30 women, mean age 37.2 (4-73) years). The average total cholesterol level in plasma was 308 mg/dl (average LDL-cholesterol 242 mg/dl), which was 116 mg/dl (120 mg/dl) above the 50th percentile of the age and sex-matched controls reported in the LRC population studies (Lipid Research Clinics' Program 1980). Tendon xanthoma and arcus lipoides were present in 25.9% and 22.2% of the patients, respectively. Plaques in the carotid arteries, determined by duplex scanning, were present in 38.9%, and coronary artery disease was present in 22.2%. This study shows that the combination of tendon xanthoma, arcus lipoides and premature atherosclerosis is no longer totally appropriate for the diagnosis of familial hypercholesterolemia (FH). It rather seems that these features are characteristic of a defective LDL receptor pathway, which could be caused by a defective LDL receptor or a defective ligand apo B100. The distinction between FH and FDB may have therapeutic implications, because certain lipid lowering drugs act by stimulation of the LDL receptor, which has a normal function in FDB.
Atherosclerosis 1992 Feb
PMID:Familial defective apolipoprotein B100: clinical characteristics of 54 cases. 163 51

In a previous study (Tybjaerg-Hansen et al, Atherosclerosis 1990;80:235-242), we identified nine patients heterozygous for the apolipoprotein B (apo B) arginine-to-glutamine (Arg3,500----Gln) mutation (familial defective apolipoprotein B-100 [FDB]). Six of these had been diagnosed clinically as familial hypercholesterolemic (FH) heterozygotes. We have since examined low density lipoprotein (LDL) receptor function in the FDB index patients and in three of their families. Skin fibroblasts from seven of seven unrelated FDB patients from whom cell lines were established exhibited normal high-affinity binding and degradation of normal LDL in vitro. In the three families, a raised plasma LDL concentration did not segregate with a haplotype of two polymorphic restriction sites at the LDL receptor locus. We conclude that the clinical and biochemical signs of classical FH can occur in the presence of the FDB mutation and a normal LDL receptor gene. In a four-generation family with 11 proven or presumed FDB heterozygotes, expression of the mutation ranged from normal plasma LDL concentrations and no clinical signs in two individuals, to hypercholesterolemia and death from myocardial infarction at age 31. Variable expression of the FDB mutation could not be explained conclusively by variation in diet, body mass index, smoking habit, apo E genotype, or plasma Lp(a) concentration.
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PMID:Clinical signs of familial hypercholesterolemia in patients with familial defective apolipoprotein B-100 and normal low density lipoprotein receptor function. 167 16

We describe a rapid screening procedure to identify known DNA sequence changes in individuals diagnosed as having heterozygous familial hypercholesterolaemia (FH). The screening is made possible by combining a rapid DNA extraction protocol and small scale polymerase chain reaction DNA amplification, followed by oligonucleotide melting or restriction enzyme digestion. We have screened for two different mutations; firstly a mutation in the apolipoprotein B (apo B) gene that results in the substitution of glutamine (Gln) for arginine (Arg) at amino acid residue 3500 (apo B3500 mutation). Apo B is the principal component of the protein moiety of low density lipoprotein (LDL) and the mutation reduces the affinity for the LDL receptor (LDL-R). Secondly we have screened for a point mutation in the LDL-R gene itself that creates a new Pst I restriction enzyme site. This mutation in the LDL-R gene (LDL-R664 mutation) results in the substitution of leucine (Leu) for proline (Pro) at amino acid 664 and is known to slow processing of the LDL-R precursor to the mature form and to reduce the affinity of the receptor on the cell surface for LDL. In 77 unrelated patients with a clinical diagnosis of FH two out of 77 (2.6%) were positive for the apo B3500 mutation. Three (3.9%) were positive for the LDL-R664 mutation. Thus these two mutations might account for 5-6% of patients in the U.K. with a clinical diagnosis of FH (5000-6000 people).(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1991 Aug
PMID:Rapid screening for specific mutations in patients with a clinical diagnosis of familial hypercholesterolaemia. 179 40

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to an increased serum level of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. It is postulated that this disorder results from a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To investigate whether recurrent mutation has contributed to the high frequency of FDB, we have conducted a haplotype analysis in previously reported and newly detected FDB heterozygotes in Germany. 5 FDB families and 6 unrelated FDB heterozygotes were genotypes at 4 polymorphic sites in the 3' end of the apo B gene. These sites consisted of the diallelic markers XbaI, MspI, EcoRI and the hypervariable region (3'HVR). In 5 FDB families and 1 unrelated FDB heterozygote the arginine(3500)----glutamine mutation could be unambiguously assigned to the haplotype XbaI-/MspI+/EcoRI-/3'HVR48, in the other 5 FDB unrelated heterozygotes this finding was consistent with the combination of the genotype. The existence of the arginine(3500)----glutamine mutation on the same and supposedly rare allele suggests that the mutant alleles are identical by descent in our population. The fact that the same mutant allele was identified in North America and Austria suggests a common European origin of the arginine(3500)----glutamine mutation.
Atherosclerosis 1991 Jun
PMID:Familial defective apolipoprotein B-100: haplotype analysis of the arginine(3500)----glutamine mutation. 189 87


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