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)

Plasma Lp(a) concentrations in newborns were quantified by a specific and sensitive ELISA assay and their evolution was followed between birth and 6 months. The influence of the diet on Lp(a) levels was also investigated. Moreover, the high sensitivity of the assay enabled the localisation of the Lp(a) fraction in the lipoprotein profile obtained after plasma separation by gel chromatography. Lp(a) levels are low at birth and rise significantly between 0 and 7 days post partum; in this newborn population, a continuous rise of the mean Lp(a) levels was observed until 180 days, in contrast with the apo B concentration that plateaus after 7 days. An early screening enabled the detection of newborns with elevated Lp(a) levels compared to the mean value of their age group. A further follow-up of some cases at 16 months confirmed the high Lp(a) levels measured in the infants and at least one of the parents. The investigation of the lipoprotein profiles as a function of the age of the newborn enabled an estimation of the size and distribution of the Lp(a) lipoprotein in four infants. At birth, Lp(a) particles were larger than LDL and tend to become more heterogeneous with increasing age of the newborn. We could not observe any statistically significant influence of the nutritional factors on the plasma Lp(a) concentrations at any age.
Atherosclerosis 1991 Feb
PMID:Lipoprotein(a) profiles and evolution in newborns. 183 63

The purpose of this study was to compare the relative effect of n-3 fatty acids on plasma lipids and platelet function in normolipemic subjects (n = 8) with plasma Lp(a) levels greater than 30 mg/dl and normolipemic subjects (n = 7) without detectable plasma Lp(a) concentrations. Six weeks of dietary supplementation (3.8 g EPA and 2.9 g DHA/d) significantly reduced (P less than 0.005) plasma TGs in both groups whereas no changes of plasma TC, LDL-C, HDL-C, and Lp(a), respectively, were found. Collagen- or thrombin-stimulated platelet aggregation and collagen- or thrombin-induced TXB2 generation from platelets decreased by approx. 45% in Lp(a)-negative and Lp(a)-positive platelet donors after a 6 week dietary intake. Four more weeks without n-3 supplementation restored the pretreatment values of TGs, platelet aggregability and TXB2 release. The biophysical properties of platelets from normolipemics with and without high plasma Lp(a) concentrations revealed a similar structural order of platelets at 37 degrees C using DPH, TMA-DPH, or 6-AS as fluorescent probes. Also similar temperature-dependent changes in platelet fluidity from 37 degrees C to 17 degrees C were observed in platelet preparations from Lp(a)-positive and Lp(a)-negative subjects. However, no subtle changes in the structural order of platelets due to nutrient intakes were found in all subjects (n = 15, 19-28 yrs) using fluorescence polarization technique. The present data suggest a similar in vitro platelet behaviour from normolipemic subjects with and without high plasma levels of Lp(a) (which is considered a risk for premature atherosclerosis) in contrast to platelet aggregability and platelet fluidity in certain hyperlipidemic stages.
Atherosclerosis 1991 Jun
PMID:Effects of dietary fish oil supplementation on platelet aggregability and platelet membrane fluidity in normolipemic subjects with and without high plasma Lp(a) concentrations. 183 37

A high plasma concentration of lipoprotein(a) [Lp(a)], a complex of low-density lipoprotein linked by disulphide bridges to apoprotein(a), is correlated with premature atherosclerosis. We determined whether the serum Lp(a) concentration could be decreased in vitro and in vivo by the reducing agent N-acetylcysteine (NAC), a drug used as a mucolytic agent, which acts by cleaving disulphide bonds. High concentrations of NAC (greater than or equal to 8 mg ml-1) resulted in dissociation of the Lp(a) antigen in vitro. However, the plasma level of Lp(a) was not changed by administration of NAC 1.2 g d-1 for 4 weeks in 7 subjects with a median Lp(a) concentration of 14.3 mg dl-1 (range 2.1-21.0 mg dl-1) or by doubling the dose to 2.4 g d-1 for a further 2 weeks. In 12 subjects with a high plasma level of Lp(a), median 87.0 mg dl-1 (range 42.0-201.6 mg dl-1), a small but significant decrease in Lp(a) concentration of 7% (P = 0.02) was observed after administration of NAC in a dose of 1.2 g d-1 for 6 weeks. These results indicate that NAC has only a limited capacity to reduce the concentration of Lp(a), which is not clinically significant.
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PMID:N-acetylcysteine and serum concentrations of lipoprotein(a). 183 21

Lipoprotein(a) is a dimer consisting of one low density lipoprotein molecule joined by a disulfide bridge to apolipoprotein(a). Apo(a) shows a considerable structural homology to plasminogen, the zymogen of the proteolytic enzyme plasmin, which dissolves fibrin clots. Apo(a) may compete with plasminogen in several manners, but itself displays no proteolytic activity. It therefore may potentially interfere with fibrinolysis. On the other hand it may also be atherogenic, as indicated by its presence in atherosclerotic plaques. Although lipoprotein(a) consists of one molecule of LDL it does not appear to be regulated by the same mechanism as LDL. Likewise, cholesterol feeding does not appear to increase levels of Lp(a), although it does increase levels of LDL cholesterol. In addition, most lipid regulating drugs that do have an effect on lowering LDL cholesterol levels have little effect on Lp(a) thus also indicating regulation under different metabolic control. Lp(a) seems to constitute a genetic risk factor for coronary atherosclerosis which is independent of all other parameters and of exogenous factors.
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PMID:[Lipoprotein (a)--link between lipid metabolism and coagulation system?]. 183 45

In a group of 303 healthy Caucasian adults of both sexes we studied the influence of the apolipoprotein E (apo E) polymorphism on plasma levels of Lipoprotein(a) (Lp(a). The APOE*2 allele was found to decrease the mean plasma Lp(a) level by 24.8%, whereas the APOE*4 allele increased the mean Lp(a) level by 25.7%. These effects were parallel to the effect of apo E polymorphism on plasma cholesterol and low density lipoprotein (LDL)-cholesterol. For the Lp(a) levels, the genetic variance associated with the APOE locus contributed about 4% to the total phenotypic variance. For plasma cholesterol and LDL-cholesterol this contribution was 4.5 and 6.3%, respectively. We also found a significant positive correlation between LDL-cholesterol and Lp(a) levels. Since the apo E polymorphism effects LDL-receptor activity, we conclude that, at least in healthy normolipidemic individuals, plasma levels of Lp(a) are modulated by the LDL-receptor activity.
Atherosclerosis 1991 Oct
PMID:Apolipoprotein E polymorphism affects plasma levels of lipoprotein(a). 183 47

To prospectively assess the role of lipoprotein(a) (Lp(a)) as a risk factor for coronary heart disease, the serum Lp(a) concentration was determined in 130 subjects without coronary events and in 138 patients in whom coronary events (i.e. fatal and non-fatal myocardial infarction and cardiac death) occurred during the 5-year Helsinki Heart Study. The participants of this study (n = 4081) were 40-55-year-old men who were devoid of coronary heart disease at the beginning of the trial; half were randomized to gemfibrozil and the other half to placebo treatment. In patients with coronary events blood pressure and total cholesterol were not significant predictors of the events but their LDL cholesterol was higher than compared to the control group in this cohort (P less than 0.05). The serum Lp(a) concentration was determined by immunoassay from samples obtained 3 months after the beginning of the trial and then stored at -20 degrees C until analysed. Studies on the effect of long term storage at -20 degrees C on serum Lp(a) levels did not reveal significant changes in Lp(a) concentration in sera stored for up to 8.5 years. The distribution of Lp(a) concentrations were similar in the men with coronary events and the controls. Nor did the mean or median levels of Lp(a) differ significantly between the two groups. Measurements of Lp(a) levels in fresh samples using 2 different immunoassays did not reveal any significant difference between the participants who had survived a myocardial infarction or participants without cardiac events. Thus, we conclude that in the Helsinki Heart Study cohort the serum Lp(a) level was not a predictor of future coronary events.
Atherosclerosis 1991 Jul
PMID:Lipoprotein (a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. 153 28

Thrombotic occlusion is the major cause of myocardial infarction (MI), and fibrin accumulation appears to play a significant role in development of atherosclerotic lesions. Any factor that reduces the lysis of fibrin may thus increase the risk of MI, and it has been suggested that this accounts for the atherogenicity of the lipoprotein variant Lp(a). The characteristic feature of Lp(a) is an apoprotein which is homologous with part of the plasminogen molecule, and experiments in vitro suggest that it interferes with uptake and activation of plasminogen on cell surfaces and fibrin. The presence of Lp(a) also seemed to offer an explanation for the apparent absence of plasminogen from 70-80% of intimal samples. We have compared the levels of Lp(a) and plasminogen in normal intima and atherosclerotic lesions. In aortic intima there was no relation between Lp(a) and plasminogen, which was absent in some samples with no Lp(a), and present in others with high levels. In intravascular thrombi plasminogen was present at a rather constant concentration (16.3 +/- 4.6 micrograms/100 mg wet tissue), whereas Lp(a) varied over a 100 fold range (0-104 micrograms/100 mg). Plasminogen binds to fibrin and is activated on the fibrin clot, so levels in extracts may not fully represent Lp(a)/plasminogen interactions. After extraction the residual tissues and thrombi were treated with 1 M epsilon-aminocaproic acid (epsilon-aca) to elute lysine-bound components. Lp(a) was eluted from all but one intimal sample, confirming previous findings on its binding to fibrin in lesions, but there was no relation between the amounts of Lp(a) and plasminogen in the tissue eluates. Paradoxically, in the thrombi there was a weak positive correlation between Lp(a) and plasminogen in epsilon-aca eluates (r = 0.504, P = 0.05). These results do not support the hypothesis that Lp(a) displaces plasminogen in vivo, but the large amount of Lp(a) eluted by epsilon-aca suggests that its atherogenicity resides in preferential binding to fibrin, leading to increased lipid accumulation in lesions.
Atherosclerosis 1991 Aug
PMID:Does lipoprotein(a) (Lp(a)) complete with plasminogen in human atherosclerotic lesions and thrombi? 183 24

Northern blotting and hybridisation with specific probes was used to detect and quantitate apolipoprotein(a) (apo(a)) mRNA in total RNA isolated from 25 human liver samples. A total of 14 different transcripts were identified suggesting that there are at least 15 different alleles at the apo(a) locus including a probable null allele. Apo(a) mRNA sizes were linearly correlated with the electrophoretic mobility of plasma apo(a) glycoprotein isoforms, and differed, in many cases, by the equivalent of one Kringle 4 unit. To investigate the relationship between apo(a) mRNA size and its concentration in the liver, and between hepatic apo(a) mRNA concentration and plasma lipoprotein(a) (Lp(a)) levels, apo(a) mRNA was quantified by densitometric scanning of autoradiograms of Northern blots. Overall, there was a significant inverse correlation between apo(a) mRNA size and its concentration in the liver, despite a marked interindividual variability in the relative amounts of similar-sized transcripts. In each heterozygous individual, the difference in concentration between the two mRNA species was determined by the difference in size. However, there was not a significant relationship between hepatic apo(a) mRNA concentration and plasma Lp(a) levels in this group. These findings emphasise the importance of mechanisms other than the rate of transcription of the apo(a) gene in the regulation of Lp(a) synthesis.
Atherosclerosis 1991 Nov
PMID:Detection and quantitation of apolipoprotein(a) mRNA in human liver and its relationship with plasma lipoprotein(a) concentration. 183 19

Atherosclerosis is the leading cause of death in the United States. Elevated plasma levels of low-density lipoprotein and lipoprotein(a) [Lp(a)] and subnormal levels of high density lipoprotein are risk factors in atherosclerotic coronary heart disease. Extracorporeal methods of affecting these risk factors are reviewed. The limited information on the effects of apheresis procedures on Lp(a) is discussed and extended from a kinetic modeling approach. An estimate, made of the number of patients who could be expected to benefit from extracorporeal lipid lowering, is presented.
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PMID:Extracorporeal methods in lipid reduction pursuant to improvement in risk factors associated with atherosclerosis. 184 63

Hyperlipidemia poses a risk for cardiovascular disease in both hemodialysis and renal transplantation patients. Although lipid profiles differ between the 2 populations, we evaluated the possibility that both groups have similar abnormalities of lipoprotein(a) [Lp(a)]. Mean serum Lp(a) and standard error of the mean (SEM) in hemodialysis and transplant recipients was 16.6 +/- 4.7 and 18.3 +/- 3.6 mg/dl, respectively, compared with 10.7 +/- 4.1 mg/dl in healthy controls, p less than 0.05. That serum Lp(a) levels are significantly elevated in dialysis and renal transplantation patients suggests at least 1 common pathogenic mechanism for the high incidence of atherosclerosis in both groups.
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PMID:Elevated lipoprotein(a) levels in renal transplantation and hemodialysis patients. 184 Feb 33


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