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)

The Ath-1 gene determines the levels of high density lipoprotein (HDL) lipid in response to a high fat diet challenge as well as susceptibility to diet-induced atherosclerosis in mice (Paigen et al. 1987. Proc. Natl. Acad. Sci. USA. 84: 3763-3767). As yet, the identity of the Ath-1 gene and how it acts to affect HDL levels are completely unknown. In an effort to clarify the nature of the gene, we have examined HDL phenotypes in strains carrying either the susceptible or resistant alleles. When challenged with a high fat diet, the susceptible strain C57BL/6 exhibited a marked decrease in the levels of HDL cholesterol and apolipoprotein A-I (apoA-I), the major protein of HDL, whereas the resistant strains C3H and BALB/c maintained high levels of both. Separation of HDL subfractions by polyacrylamide gradient gel electrophoresis revealed that the decrease was particularly striking among the larger HDL species. The rates of synthesis of apoA-I in liver and intestine were similar in the strains and were unaffected by the high fat diet. Although the rates of synthesis of apoA-II and the levels of apoA-II mRNA were decreased in response to the high fat diet, similar decreases were observed in both the susceptible and resistant strains. We conclude that the Ath-1 gene results in a rapid decrease in both HDL lipid and HDL apolipoprotein levels in the susceptible strain in response to the high fat diet and that this is mediated primarily at the level of HDL catabolism.
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PMID:Phenotypic characterization of the Ath-1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis. 210 72

Mouse plasma from strains C57BL/6J and C3H/HeJ includes a high density lipoprotein (HDL) fraction containing apolipoprotein A-I which migrates in the prebeta region upon agarose gel electrophoresis, similar to the prebeta HDL previously reported in humans. This prebeta A-I lipoprotein species has a buoyant density of 1.080-1.210 g/ml and has two molecular weight species, 65,000 and 71,000. It is lipid-poor and deficient in apolipoprotein E. When mice are fed a high fat and high cholesterol diet, the quantity of prebeta A-I increases in both strains as determined by quantitative densitometry of agarose gel immunoblots. Prebeta A-I species are highly unstable in plasma at 37 degrees C. Initially (0-1 h) levels decreased and with further incubation (1-8 h) levels increased. Nondenaturing polyacrylamide gel electrophoresis (PAGE) demonstrated that the prebeta HDL formed during prolonged incubation (1-8 h) was identical in size to HDL in unincubated samples. The initial decrease of prebeta HDL observed during the first hour of incubation, phase I, was inhibited by DTNB, suggesting that phase I is dependent on lecithin:cholesterol acyltransferase (LCAT); however, the subsequent increase, phase II, was unaffected by DTNB and appears LCAT-independent. The prebeta A-I species formed in plasma containing DTNB after a 4-h incubation resulted in a polydisperse particle size distribution. The two strains, the atherosclerosis-susceptible C57BL/6 and -resistant C3H, displayed a similar elevation and induction of prebeta HDL during a dietary switch from laboratory chow to an atherogenic diet with a transient peak occurring at 7 days even when total HDL in the susceptible strain was greatly reduced.
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PMID:Interconversion of prebeta-migrating lipoproteins containing apolipoprotein A-I and HDL. 210 30

To investigate the prostaglandin I2 (PGI2) half-life regulated by high density lipoprotein (HDL) in patients with coronary artery disease (CAD), we determined the stability of PGI2 and serum apolipoprotein A-I (Apo A-I) and apolipoprotein A-II (Apo A-II) levels in four age-matched groups of patients: controls (n = 17), angina pectoris (n = 18), unstable angina pectoris (n = 17), myocardial infarction (n = 19) (acute phase, 3.6 +/- 1.7 hours from onset; subacute phase, 75 +/- 15 hours from onset in the same patients). Serum PGI2 half-life and total serum Apo A-I levels were lower in the CAD group than in the control group. PGI2 was least stable in patients with unstable angina and the acute phase of myocardial infarction. In these patients, the molar ratio of Apo A-I to Apo A-II and HDL-associated Apo A-I levels were decreased, and free Apo A-I levels were increased. After in vitro incubation of HDL with increasing amounts of Apo A-II, Apo A-I in HDL was displaced by Apo A-II, with the parallel decrease in stability of PGI2. Free Apo A-I cannot stabilize PGI2. HDL-associated Apo A-I, whose amount is affected by Apo A-II, stabilized PGI2 and correlated well with stability of PGI2 in patients with CAD and control patients. Decreased PGI2 half-life may play an important role in the pathogenesis of atherosclerosis and thrombus formation in the coronary arteries, especially thrombus formation during an acute coronary event.
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PMID:Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris. 211 45

The correlations between lipid and lipoprotein measurements and other risk factors of coronary artery disease were evaluated in 101 men undergoing coronary angiography. Clinically significant disease was present in 75 patients, whereas 24 had no observable lesions and 2 had minimal lesions. Comparisons of individual lipid and lipoprotein levels were nearly all significantly different between patients with and patients without clinically significant disease; however, no single variable could predict the presence of disease among patients. Logistic regression analysis identified five factors: apolipoprotein A-I, apolipoprotein B, diabetes, age, and family history of heart disease, which account for most of the differences between the two patient groups. These results could have important implications for the evaluation and management of patients suspected of having coronary atherosclerosis.
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PMID:Correlates of atherosclerosis in coronary arteries of patients undergoing angiographic evaluation. 211 60

Although of great clinical and biological importance, the role of genotype-diet interaction in lipoprotein metabolism and atherosclerosis is still poorly understood. We analyzed serum apolipoprotein A-I (apo A-I) concentrations of approximately 600 pedigreed baboons that were fed two dietary regimens: (1) a basal diet and (2) an atherogenic (high-cholesterol, saturated-fat) diet. Complex segregation analysis was performed separately for apo A-I concentrations in each dietary environment. A major locus model with a recessive allele for high levels of apo A-I and a polygenic component best fit the family data for both diets. Using bivariate segregation analysis, we showed that the major genes detected in the univariate analyses represent two distinct loci that act additively to determine apo A-I concentrations. These two loci accounted for approximately 40% of the total phenotypic variance in apo A-I levels in each dietary environment and were also responsible for 33% of the variation in apo A-I response to the atherogenic diet. Both major loci were influenced by genotype-diet interaction in which the two-locus genotypes exhibited heterogeneous responses to the atherogenic diet. Most genotypes responded to the atherogenic diet with an increase in apo A-I, but two genotypes showed a decrease that can be traced to the effect of one of the major loci. The presence of two major loci and genotype-diet interaction may be responsible for the equivocal results obtained in human pedigree studies of apo A-I.
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PMID:Genetic analysis of apolipoprotein A-I in two dietary environments. 211 6

Apolipoprotein A-I, the major protein of high-density lipoproteins, and apolipoprotein B, the major protein of low-density lipoproteins can serve as important predictor of the risk of cardiovascular diseases. The lack of an internationally valid standardization is a serious impediment to a broad application of the apolipoprotein measurements in the laboratory diagnosis of atherosclerosis. A common effort is at the present made by the IFCC Committee on Apolipoproteins together with several commercial organizations to achieve a consensus on a practical standardization procedure for the measurement of apolipoprotein A-I and B. The aim is a) to calibrate all commercially available Apo A-I and Apo B test kits using frozen serum pools previously standardized against primary reference materials and b) to select the secondary serum reference preparations which will substitute the frozen serum pools and will be used for the control of the validity of the own calibration. The available results from a preliminary exercise prove with a variation less than 5% for Apo A-I and less than 8% for Apo B with patients' samples that the use of common reference materials leads to the harmonization of the results obtained with different test systems for measurement of apolipoprotein A-I and B.
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PMID:[Standardization of the immunochemical detection of apolipoprotein A-I and B]. 212 24

Nine patients with type III hyperlipoproteinaemia and homozygosity for the apolipoprotein E2 isoform were treated with 15 g daily of MaxEPA, a fish oil preparation rich in eicosapentaenoic acid (2.7 g daily) and docosahexaenoic acid (1.8 g daily) for 16 weeks. Plasma lipoprotein and apolipoprotein concentrations were compared with those obtained during treatment with an olive oil preparation. MaxEPA treatment decreased plasma median total cholesterol, triglyceride and apolipoprotein B concentrations by 16, 53 and 19%, respectively. Plasma median very low density lipoprotein (VLDL)-cholesterol, triglyceride and apolipoprotein B concentrations were reduced by 45, 62 and 75% respectively, while the abnormal VLDL-cholesterol/triglyceride ratio remained unchanged. Individual reductions of VLDL concentrations varied considerably, for VLDL-cholesterol between 10 and 75%. In the majority of cases the abnormal late pre beta-bands on agarose electrophoresis, typical for type III hyperlipoproteinaemia normalized to pre beta-mobility on MaxEPA treatment. LDL-cholesterol and apolipoprotein B tended to increase after 8 weeks on MaxEPA but decreased again after 16 weeks. Median plasma high density lipoprotein cholesterol and apolipoprotein A-I did not change during MaxEPA treatment. It is concluded that MaxEPA have decreasing effects on plasma VLDL lipid and apolipoprotein concentrations in apolipoprotein E2 homozygous type III hyperlipoproteinaemia but that this effect is variable and unpredictable.
Atherosclerosis 1990 Feb
PMID:Effect of fish oil treatment on plasma lipoproteins in type III hyperlipoproteinaemia. 213 96

The effect of two oral contraceptives containing 30 micrograms ethinylestradiol + 75 micrograms gestodene (EE/GSD) or 30 micrograms ethinylestradiol + 150 micrograms desogestrel (EE/DG) upon serum lipids and lipoproteins were measured in 11 women each on days 1, 10, and 21 of the first, third, sixth, and twelfth treatment cycle and compared to the levels on days 1, 10, and 21 of the preceding control cycle. There was no change in total cholesterol (CH) and phospholipids (PL), while total triglycerides (TG) were significantly elevated only during treatment with EE/GSD. After 3 and 6 months of intake of both oral contraceptives, a transitory increase in the TG content of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), and a decrease in LDL-PL was observed. After 12 months, VLDL-CH, VLDL-PL, and apolipoprotein B were significantly elevated, while VLDL-TG and all components of LDL were unchanged. Most of the components of high-density lipoprotein (HDL) were increased due to a rise in HDL3 and apolipoprotein A-II, while HDL2 and apolipoprotein A-I were not altered. There was no significant difference between the effects of the two preparations, although those of EE/GSD were mostly more pronounced. The time-dependent change in the effects of the oral contraceptives on various parameters of lipid metabolism demonstrates that the relevance of results of short-time studies may be questionable. There was also a significant alteration in some parameters between day 1 and 10 of the treatment cycles and a tendency to return to the pretreatment levels during the pill-free week, e.g., in total TG and in the PL component of VLDL, LDL and HDL. The increase in HDL, VLDL, and total TG reflects a slight preponderance of the effect of ethinylestradiol on lipid metabolism. The unchanged total CH and LDL-CH and the elevated HDL levels indicate that the risk of the development of atherosclerosis is in all probability not increased during treatment with both preparations.
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PMID:Changes in lipid metabolism during 12 months of treatment with two oral contraceptives containing 30 micrograms ethinylestradiol and 75 micrograms gestodene or 150 micrograms desogestrel. 213 73

The association of insulin with cardiovascular disease (CVD) may be mediated in part by the associations of insulin with CVD risk factors, particularly blood pressure and serum lipids. These associations were examined in 4576 black and white young adults in the CARDIA Study. Fasting insulin level was correlated in univariate analysis with systolic blood pressure (r = 0.16), diastolic blood pressure (r = 0.13), triglycerides (r = 0.27), total cholesterol (r = 0.10), high density lipoprotein (HDL) cholesterol (r = -0.25), and low density lipoprotein (LDL) cholesterol (r = 0.14), and with age, sex, race, glucose, body mass index, alcohol intake, cigarette use, physical activity, and treadmill duration (all p less than 0.0001). After adjustment for these covariates, insulin remained positively associated with blood pressure, triglycerides, total and LDL cholesterol, and apolipoprotein B and was negatively associated with HDL, HDL2 and HDL3 cholesterol, and apolipoprotein A-I in all four race-sex groups. Higher levels of fasting insulin are associated with unfavorable levels of CVD risk factors in young adults; these associations, though relatively small, can be expected to increase the risk of atherosclerosis. Demonstration of these relationships in a large, racially diverse, healthy population suggests that insulin may be an important intermediate risk factor for CVD in a broad segment of the U.S. population.
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PMID:Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA study. 218 41

Plasma lipids and apolipoproteins were quantified in two kindreds of hypobetalipoproteinemia. All affected members were asymptomatic but showed a decrease of 75% in apolipoprotein B and of 69% in LDL-cholesterol. There were no major changes in apo A-I and A-II but all affected family members had reduced levels of apo C-II (by 58%) and C-III (by 59%) without significant decrease in apo C-I and no specific decrease of apo C-III1. Apolipoprotein E is decreased in SDS-PAGE. The plasma level and phenotype of Lp(a) are not affected by HBL, suggesting that a catabolic rather than a synthetic mechanism is responsible for the disease. As shown by density gradient ultracentrifugation, HDL2 particles that contain essentially apolipoprotein A-I, cholesterol and phospholipids represent in affected subjects the major part of HDL. Due to the net reduction of apolipoprotein B-containing particles (VLDL and LDL) as acceptors of lipids in HBL, there is an accumulation of large particles rich in cholesteryl esters.
Atherosclerosis 1990 Aug
PMID:Plasma lipids, lipoproteins and apolipoproteins in two kindreds of hypobetalipoproteinemia. 224 96


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