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)

Rats with alloxan-induced diabetes developed severe atherosclerotic lesions when they were maintained on a 0.25% cholesterol diet for one year. The atheromatous changes developed at the aortic arch, appeared as early as 3 months after the start of the experiment, and increased thereafter. The diabetic rats also developed atherosclerosis when they were fed standard rat chow, but the area of the atheromatous lesion was about one tenth of that in rats fed the high-cholesterol diet. Normal rats did not develop atherosclerosis even when fed the high-cholesterol diet for one year. The alloxan diabetic rats showed no increase in body weight, but developed serum glucose levels as high as 600-800 mg/dl as well as high serum cholesterol levels and lower serum HDL-cholesterol levels. The development of atherosclerosis in these rats was significantly related to an increase in the serum cholesterol/phospholipid ratio, the atherogenic index (TC-HDLC/HDLC), and the serum total cholesterol level, but was not related to the serum glucose, HDL-cholesterol, triglyceride, or lipid peroxide levels. These relationships were found as early as B-16 weeks after the start of the experiment. These data suggest that the serum cholesterol/phospholipid ratio, the atherogenic index, and the total cholesterol level are important risk factors for the development of atherosclerosis in rats with alloxan diabetes.
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PMID:Development of atherosclerosis in alloxan diabetic rats. 922 80

Abnormal cholesterol fraction is an essential risk factor for atherosclerosis of large cerebral arteries in young Asians. In order to reduce the medical cost and social resource for cholesterol electrophoresis, especially in undeveloped and developing Asian countries, we evaluated the validity of Nanji's GUT score for predicting TC: HDLC ratio in this population. Results showed that GUT score only predicted 71% of them. We also tested the predictive power of CUT index, and predicting rate was 81%. Therefore, Nanji's GUT score is not an ideal surrogate for cholesterol electrophoresis. We recommend CUT index to screen for high-risk subjects till a new method can satisfy the economic pattern in Asian countries.
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PMID:Prediction of total cholesterol: high-density-lipoprotein-cholesterol ratio in young adults. 944 31

High density lipoproteins (HDL) encompass structurally and functionally heterogeneous particles. Two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) and subsequent immunoblotting helps to differentiate quantitatively minor HDL-subclasses from the bulk of HDL, which contains apo A-I and has electrophoretic alpha-mobility. Pulse-chase experiments identified the quantitatively minor HDL subclasses prebeta1-LpA-I, gamma-LpE and LpA-IV as initial and fast acceptors of cell-derived cholesterol and alpha-migrating HDL (i.e. alpha-LpA-I) as a late and slow acceptor. In plasmas of patients with certain forms of familial HDL-deficiency such as apo A-I deficiency and Tangier disease, prebeta1-LpA-I, gamma-LpE and LpA-IV represent the only HDL particles and account for the significant residual cholesterol efflux capacity of these plasmas. These particles, however, also fulfill important roles in reverse cholesterol transport of normal plasma. Prebeta1-LpA-I, for example, is generated, during the interconversion of HDL by lipid transfer proteins. Thus, incubation of plasma with phospholipid transfer protein increases the concentration of prebeta1-LpA-I and in parallel increases the cholesterol efflux capacity of plasma indicating that lipid transfer proteins modulate cholesterol efflux by modification of HDL subclass composition. Apo E and gamma-LpE are of special interest for reverse cholesterol transport since macrophages can produce apo E.
Atherosclerosis 1998 Apr
PMID:High density lipoproteins and reverse cholesterol transport: lessons from mutations. 969 35

The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density lipoprotein deficiency and Tangier disease. We report the complete human ABCA1 gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and exons, and 1 kb of the 3' flanking region. The ABCA1 gene spans 149 kb and comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns 1-49. The transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1 protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5' upstream of the transcriptional start site reveals multiple binding sites for transcription factors with roles in lipid metabolism. Comparative analysis of the mouse and human ABCA1 promoter sequences identified specific regulatory elements, which are evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings provide insights into ABCA1-mediated regulation of cellular cholesterol metabolism and will facilitate the identification of new pharmacologic agents for the treatment of atherosclerosis in humans.
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PMID:Complete genomic sequence of the human ABCA1 gene: analysis of the human and mouse ATP-binding cassette A promoter. 1088 28

The proportions of plasma high and low density lipoprotein cholesterol have been linked to inherited tendency for atherosclerosis in humans. Studies were conducted with Japanese quail males from lines genetically selected for high and low TC and a randombred (unselected) control line that were fed 0.0 or 0.5% cholesterol for 12 weeks. Atherosclerotic plaques were more severe in the high than in the low line quail and in those fed cholesterol compared to non-cholesterol-fed quail. Serum TG, TC, VLDLC, LDLC, and HDLC were also higher in the high than in the low line quail and in cholesterol-fed vs. non-cholesterol-fed quail. Significant interactions indicated that TC and LDLC concentrations were more affected by dietary cholesterol in the high line than in the low line. The low line quail maintained higher HDLC and lower LDLC than the high line. Regression and correlation analyses revealed that although VLDLC, LDLC, and TC were significant predictors of atherosclerosis in the high line birds, the TC/HDLC ratio was a better predictor in the low line. The Japanese quail lines used herein represent useful experimental models for studies of genetic differences in atherosclerosis in humans.
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PMID:Total cholesterol, total triglycerides, and cholesterol distribution among lipoproteins as predictors of atherosclerosis in selected lines of Japanese quail. 1124 92

Mutations in the ATP-binding cassette transporter 1 (ABCA1) gene have been recently identified as the molecular defect in Tangier disease (TD) and familial high density lipoprotein deficiency (FHA). We here report novel mutations in the ABCA1 gene in two sisters from a Japanese family with TD who have been described previously (S. Ohtaki, H. Nakagawa, N. Kida, H. Nakamura, K. Tsuda, S. Yokoyama, T. Yamamura, S. Tajima, A. Yamamoto, Atherosclerosis 49 (1983)) and a family with FHA. Both probands of TD and FHA developed coronary heart disease. Sequence analysis of the ABCA1 gene from the patients with TD revealed a homozygous G to A transition at nucleotide 3805 of the cDNA resulting in the substitution of Asp 1229 with Asn in exon 27, and a C to T at nucleotide 6181 resulting in the substitution of Arg 2021 with Trp in exon 47. Sequence analysis of the ABCA1 gene from the FHA patient revealed a homozygous 4 bp CGCC deletion from nucleotide 3787 to 3790 resulting in premature termination by frameshift at codon 1224. These mutations were confirmed by restriction digestion analysis, and were not found in 141 control subjects. Our findings indicate that mutations in the ABCA1 gene are associated with TD as well as FHA.
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PMID:Novel mutations in ABCA1 gene in Japanese patients with Tangier disease and familial high density lipoprotein deficiency with coronary heart disease. 1147 65

Although androgenic hormones decrease HDLC concentration, no direct evidence has linked them to atherosclerosis. The present study was undertaken to extend our ability to assess risk associated with androgen induced lipoprotein(Lp) changes by simultaneously gathering information about postprandial triglyceridaemia (PPT), LDL particle size, HDL and Lp(a) in men either taking exogenous androgens or with suppressed endogenous androgen concentrations. The experimental groups comprised nine male bodybuilders who self-administered anabolic-androgenic steroids (AAS) for a mean period of 6.5 weeks, and 10 healthy men whose testosterone concentration had been reversibly suppressed for 5 weeks using the GnRH agonist triptorelin (Decapeptyl; D-Trp-6-LHRH). A separate group receiving no hormonal treatment provided analytical control (n=7). Lipoprotein size was assessed by gradient gel electrophoresis categorisation (GGE), lipoprotein concentrations by immuno and enzymatic assays and PPT by a standardised oral fat tolerance test (65g /m(2)). Testosterone concentration was significantly reduced on triptorelin from 7.32+/-1.92 to 1.15+/-0.57 ng/ml (P=0.002). High dose AAS use was confirmed by urinalysis. With AAS use, mean HDLC and Lp(a) concentrations and PPT decreased from 0.9+/-0.3 to 0.7+/-0.3 mmol/l (P=0.004), 125+/-128 to 69+/-73 U/l (P=0.008) and 11.6+/-10.0 mmol/l h to 7.5+/-5.4 mmol/l h (P=0.027) respectively. Mean total cholesterol and LDLC were unchanged. LDL size was unchanged in six AAS users, decreased in one but remaining in the normal size range, and increased in two from small LDL to the normal range. Size changes in the latter two subjects were associated with 42 and 58% reductions in PPT respectively. In the triptorelin group, mean total cholesterol, HDLC and Lp(a) were increased from 4.8+/-0.8 mmol/l to 5.2+/-1.0 mmol/l (P=0.039), 1.1+/-0.2 to 1.4+/-0.3 mmol/l (P=0.002) and 278+/-149 to 377+/-222 U/l (P=0.004) respectively. Mean LDLC concentration and PPT were unchanged. LDL particle size increased in four, decreased in two, and was unchanged in four subjects. LDL size decreased in two and showed no change in the other five control subjects. Other lipid measures were unchanged in the control group. Thus, apart from lowering HDLC concentrations, no other potentially atherogenic effects of endogenous androgens or AAS were observed. A suppression of Lp(a) as well as a reduced PPT and increased LDL size in predisposed individuals may be antiatherogenic effects of AAS.
Atherosclerosis 2001 Dec
PMID:Effects of androgen manipulation on postprandial triglyceridaemia, low-density lipoprotein particle size and lipoprotein(a) in men. 1173 Aug 23

The ATP-binding cassette transporter 1 (ABCA1) has recently been identified as a key regulator of high-density lipoprotein (HDL) metabolism, which is defective in familial HDL-deficiency syndromes such as Tangier disease. ABCA1 functions as a facilitator of cellular cholesterol and phospholipid efflux, and its expression is induced during cholesterol uptake in macrophages. To assess the role of macrophage ABCA1 in atherosclerosis, we generated low-density lipoprotein (LDL) receptor knockout (LDLr(-/-)) mice that are selectively deficient in leukocyte ABCA1 (ABCA1(-/-)) by using bone marrow transfer (ABCA1(-/-) --> LDLr(-/-)). Here we demonstrate that ABCA1(-/-) --> LDLr(-/-) chimeras develop significantly larger and more advanced atherosclerotic lesions compared with chimeric LDLr(-/-) mice with functional ABCA1 in hematopoietic cells. Targeted disruption of leukocyte ABCA1 function did not affect plasma HDL cholesterol levels. The amount of macrophages in liver and spleen and peripheral blood leukocyte counts is increased in the ABCA1(-/-) --> LDLr(-/-) chimeras. Our results provide evidence that leukocyte ABCA1 plays a critical role in the protection against atherosclerosis, and we identify ABCA1 as a leukocyte factor that controls the recruitment of inflammatory cells.
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PMID:Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. 1197 62

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in western societies. Although cholesterol is a major cardiovascular disease risk factor, therapeutic interventions to lower plasma cholesterol levels have had limited success in reducing coronary events, underscoring the need for other treatment strategies. A promising therapeutic target is an ATP binding cassette transporter called ABCA1, a cell membrane protein that is the gatekeeper for secretion of excess cholesterol from macrophages into the high-density lipoprotein (HDL) metabolic pathway. Mutations in ABCA1 cause Tangier disease, a severe HDL-deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. Thus, ABCA1-activating drugs have the potential to mobilize cholesterol from macrophages of atherosclerotic lesions, making them powerful agents for preventing and reversing cardiovascular disease. (c) 2002 Prous Science. All rights reserved.
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PMID:ABCA1 as a New Therapeutic Target for Treating Cardiovascular Disease. 1267 41

Familial HDL deficiency (FHD) is a rare autosomal dominant lipoprotein disorder. We describe a novel genetic variant of the apolipoprotein A-I (apoA-I) gene resulting in FHD. The proband is a 51-year-old woman who was hospitalized due to severe heart failure. Her plasma HDL-cholesterol (C) and apoA-I concentrations were 0.08mmol/l and 1mg/dl, respectively. She exhibited corneal opacities and planar xanthomas on eyelids and elbows. Coronary angiography demonstrated extensive obstructions in two major vessels. Genomic DNA sequencing of the patient's apoA-I gene revealed a homozygosity for a GC deletion between 5 GC repeats in exon 4, creating a frameshift and a stop codon at residue 178. We designated this mutation as apoA-I Shinbashi. The proband's father, son, and daughter were found to be heterozygous for this mutation and their HDL-C and apoA-I levels were about half of normal levels, demonstrating a gene dosage effect. The father underwent coronary bypass surgery at age of 70 years. Lecithin-cholesterol acyltransferase (LCAT) activity was decreased by 63% in the homozygote and 31% in heterozygotes, respectively. This new case of apoA-I deficiency, apoA-I Shinbashi, is the first case involving a single gene defect of the apoA-I gene to develop all the characteristics for apoA-I deficiency, including premature coronary heart disease.
Atherosclerosis 2004 Jan
PMID:A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronary artery disease. 1470 55


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