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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent epidemiological studies have shown some beneficial health effects of the long chain (n-3) polyunsaturated fatty acids found in fatty fish. Although the results of these studies are often ambiguous and inconclusive, they have prompted many intervention trials to study the effects of n-3 fatty acids (FA) on the cardiovascular risk profile. However screening of the literature revealed that many of the beneficial effects of fish (oil) were obtained in intervention studies which had several serious shortcomings in their design. Therefore we started a placebo controlled randomised trial with increasing doses of n-3FA (respectively 0; 1.12; 2.24 and 3.37 g n-3 FA/day) and in order to have a maximum compliance this study was done in healthy monks. Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months. We couldn't detect any effect of n-3 FA supplementation on total cholesterol, HDL cholesterol, LDL cholesterol, apo A1, Lp(a), HbA1C, glucose, fibrinogen, factor VIII, antithrombin III, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor concentration, on bleeding time or on systolic or diastolic blood pressure. A pronounced significant dose dependent decrease of triglyceride levels was seen, while a slight but statistical significant decrease of apo B levels was observed in the highest fish oil dose. As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion, the clinical relevance of these finding is not clear at the moment. It seems therefore improbable that the anti-atherosclerotic action of n-3 FA is due to an effect on the lipid, apoprotein, coagulation or fibrinolysis parameters as measured in our study. Hence further research must be focused on other parameters (prostaglandins) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process.
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PMID:Influence of supplementation with N-3 fatty acids on different coronary risk factors in men--a placebo controlled study. 141 84

Exercise training alters plasma lipoprotein profiles in a manner compatible with decreased coronary artery disease risk. The aim of this study was to ascertain whether interruption of training (detraining) was associated with potentially undesirable changes in the metabolism of post-prandial lipoproteins and plasma levels of Lp(a). Eight normolipidemic, male runners who ran 30-40 miles/week were studied in the trained state and after 14-22 days of detraining. Two of the subjects were studied in the reverse order to control for any confounding effects of exercise sequence. Detraining resulted in (1) a 12% (P = 0.002) reduction in the subjects' aerobic capacity, (2) a 7.7% (P = 0.007) reduction in fasting concentrations of high density lipoprotein cholesterol (HDL-C), (3) a 21% (P = 0.01) reduction in post-heparin lipoprotein lipase activity. Lp(a) concentrations did not change significantly (mean increase 15%, P = 0.076). Fasting plasma concentrations of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) did not change in the detrained state. There was little fluctuation over 24 h in plasma concentrations of TC, LDL-C and HDL-C in either the trained or detrained states. TG concentrations fluctuated over the 24 h in accord with food intake, but there were no exercise-related changes. Exercise had a dramatic effect on chylomicron and chylomicron remnant metabolism as measured by retinyl palmitate measurements. The mean areas under the concentration vs. time curves (AUC) for chylomicron-retinyl esters increased by 41% (P = 0.013) and for chylomicron remnant-retinyl ester by 37% (P = 0.058) following detraining.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1992 Aug
PMID:Short-term interruption of training affects both fasting and post-prandial lipoproteins. 141 92

The frequency distribution for serum lipoprotein(a) (Lp(a)) concentrations in healthy Japanese was highly skewed, with a mean +/- S.D. of 14.6 +/- 13.6 mg/dl and a median of 11.0 mg/dl. The present study provides the first evidence on the frequencies of Lp(a) phenotypes and alleles in healthy Japanese subjects. There was a strong inverse relationship between the apparent molecular weights of apo(a) isoforms and plasma Lp(a) concentrations, as reported previously. However, because of the considerable overlap between the Lp(a) concentrations of the different phenotypes, it was impossible to predict Lp(a) concentration from Lp(a) phenotypes, or vice versa. The present results suggest that the distribution of Lp(a) concentrations, mean and median values and Lp(a) phenotype and allele frequencies in healthy Japanese are not significantly different from the results for Europeans, whereas they are significantly different from other Asian populations, i.e. Chinese, Indians and Malaysians.
Atherosclerosis 1992 Sep
PMID:Studies on apolipoprotein(a) phenotypes. Part 1. Phenotype frequencies in a healthy Japanese population. 141 98

In the present paper, we have evaluated serum Lp(a) concentrations, the frequencies of Lp(a) phenotypes and alleles and the association between the Lp(a) phenotypes and serum Lp(a) levels in 470 patients with angiographically defined coronary artery disease (CAD). Serum Lp(a) concentrations were significantly increased in proportion to the number of diseased vessels in the CAD patients. The frequencies of Lp(a) phenotypes in the CAD patients were significantly different from those in healthy subjects. In particular, the frequency of double-band phenotypes was higher in the CAD group. The frequencies of Lp(a) alleles in the CAD patients, however, were not significantly different from those in the healthy subjects. There was a strong inverse relationship between the apparent molecular weights of apo(a) isoforms and serum Lp(a) concentrations. Lp(a) levels in the CAD patients were higher than those in the healthy subjects with the same phenotype. The present results suggest that it is important to consider some posttranslational or environmental modifications and other factors, in addition to the genetic factor, when assessing contributions to plasma Lp(a) levels.
Atherosclerosis 1992 Sep
PMID:Studies on apolipoprotein(a) phenotypes. Part 2. Phenotype frequencies and Lp(a) concentrations in different phenotypes in patients with angiographically defined coronary artery diseases. 141 6

To investigate the role of lipoprotein (a) (Lp[a]) as an atherogenic condition related to hypercholesterolemia, we studied the serum concentration of Lp(a) as measured by immunonephelometry in relation to the presence of asymptomatic echographic plaques in the peripheral arteries of 103 untreated hypercholesterolemic, normotensive, middle-aged men. Plaque was found at carotid, aortic, and femoral sites in 36%, 51%, and 53% of subjects, respectively. The Lp(a) level was higher in the group with carotid plaques than in the group without (0.29 +/- 0.20 versus 0.17 +/- 0.14 g/l, p < 0.01), not significantly higher in the group with aortics plaque than in the group without (0.24 +/- 0.19 versus 0.19 +/- 0.16 g/l), and not different between groups with and without femoral plaques (0.21 +/- 0.18 versus 0.22 +/- 0.17 g/l). A logistic regression analysis confirmed that Lp(a) was associated with carotid plaques (p = 0.004), independent of other risk factors. However, in patients with low density lipoprotein cholesterol values above the group median value (4.7 mmol/l), Lp(a) was associated not only with carotid plaques (p < 0.01) but also with aortic plaques (p < 0.05), as well as with the number of diseased sites (p = 0.02). In contrast, in patients with low density lipoprotein cholesterol levels below or equal to 4.7 mmol/l, Lp(a) only remained associated with carotid plaques (p < 0.05). Thus, in symptom-free, hypercholesterolemic men, early atherosclerosis was influenced by serum Lp(a), particularly in the carotid arteries, as well as by the presence of a higher level of low density lipoprotein cholesterol.
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PMID:Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA Group. 142 94

We have previously shown that lipoprotein(a) [Lp(a)], an atherogenic lipoprotein that contains apolipoprotein(a), which shares partial structural homology to plasminogen, binds to a plasmin-modified fibrin surface, and we have postulated that this interaction may be atherogenic. Moderate elevations in blood homocysteine, a relatively common condition, predispose to premature atherosclerosis. The reasons for this are not established. We now report that homocysteine, at concentrations as low as 8 microM, significantly increases the affinity of Lp(a) for fibrin. Homocysteine induces a 20-fold increase in the affinity between Lp(a) and plasmin-treated fibrin and a 4-fold increase with unmodified fibrin. Lp(a) binding is inhibited by epsilon-aminocaproic acid, indicating lysine binding site specificity. Homocysteine does not enhance the binding of Lp(a) to other surface-bound proteins. Cysteine, glutathione, and N-acetylcysteine also increase the affinity between Lp(a) and fibrin. Homocysteine does not affect the binding of low density lipoprotein or plasminogen to fibrin, nor does it alter the gel-filtration elution pattern of Lp(a). Immunoblot analysis documents the fact that homocysteine partially reduces Lp(a). These results suggest that homocysteine alters the intact Lp(a) particle so as to increase the reactivity of the plasminogen-like apolipoprotein(a) portion of the molecule. The observation that sulfhydryl amino acids increase Lp(a) binding to fibrin suggests a biochemical relationship between sulfhydryl compound metabolism, thrombosis, and atherogenesis.
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PMID:Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism. 143 9

Several lipid-related reactions involving coagulation and fibrinolytic mechanisms have been described. Many of these reactions have been related to the development of atherosclerosis and thromboembolism. In this article, I review the antiphospholipid antibody syndrome, the tissue factor pathway inhibitor, the involvement of fatty acids in fibrinolysis, and the Lp(a) lipoprotein.
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PMID:Lipid-related clotting reactions of clinical significance. 145 82

Elevated plasma levels of the lipoprotein Lp(a) are associated with increased risk for atherosclerosis and its manifestations, myocardial infarction, stroke and restenosis (for reviews, see refs 1-3). Lp(a) differs from low-density lipoprotein by the addition of the glycoprotein apolipoprotein(a), a homologue of plasminogen that contains many tandemly repeated units which resemble the fourth kringle domain of plasminogen, and single homologues of its kringle-5 and protease domain. As plasma Lp(a) concentration is strongly influenced by heritable factors and is refractory to most drug and dietary manipulation, the effects of modulating it are difficult to mimic experimentally. In addition, the absence of apolipoprotein(a) from virtually all species other than primates precludes the use of convenient animal models. Here we show that transgenic mice expressing human apolipoprotein(a) are more susceptible than control mice to the development of lipid-staining lesions in the aorta, and that apolipoprotein(a) co-localizes with lipid deposition in the artery walls.
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PMID:Atherogenesis in transgenic mice expressing human apolipoprotein(a) 146 21

We examined serum lipids, lipoproteins, apolipoproteins (Apo), lipoprotein(a) (Lp(a)), C4b-binding protein (C4bp) and lathosterol in 22 normolipidemic (serum total cholesterol less than 220 mg/dl and serum triglycerides less than 150 mg/dl) male patients with coronary artery disease (CAD) and 33 normal male subjects. Many of the patients in the CAD group with normal total cholesterol (T-Ch) and triglycerides (TG) had higher TG, low-density lipoprotein (LDL)-Ch, beta-lipoprotein (Lipo) and Apo B values and lower high-density lipoprotein (HDL)-Ch, Apo A-I and Apo A-II values than those of the control group. Differences were also observed in the beta-Lipo/HDL-Ch, Apo B/Apo A-I, and HDL-Ch ratios and the atherogenic index [A.I. = (T-Ch--HDL-Ch)/HDL-Ch], all of which are generally accepted as indices for atherosclerosis. Even in CAD patients with normolipidemia, the HDL-Ch/T-Ch ratio and A.I. seemed to be important risk factors. In addition, Lp(a) and lathosterol, an accepted indicator of whole-body cholesterol synthesis, were higher in the CAD group. The CAD group also appeared to have a higher C4bp value, suggesting that this parameter is correlated with other lipids.
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PMID:Risk factors in normolipidemic male patients with coronary artery disease in Japanese. 152 95

Increased plasma levels of the apoB-100-containing lipoprotein(a) (Lp(a)) are associated with an increased risk for atherosclerosis and myocardial infarction, but the mechanisms by which lipoprotein(a) may accelerate these processes remain obscure. In this study we have investigated the impact of the association of apoprotein(a) with the low density lipoprotein (LDL)-like Lp(a) particle upon specificity of receptor recognition after lipoprotein modification by malondialdehyde or transition metal-induced oxidation. We have determined that radioiodination labels both apoprotein components of Lp(a), that malondialdehyde modification produces an anionic lipoprotein comparable to native Lp(a) in Stokes' radius, and that N,N'-disubstituted 1-amino-3-iminopropene derivatives preferentially cross-link apoprotein(a) to apoB-100 protein. Like LDL, native Lp(a) is recognized in human monocyte-macrophages by the LDL receptor. Like LDL, progressive modification of Lp(a) by malondialdehyde abolishes lipoprotein recognition by the LDL receptor and produces uptake and hydrolysis by the scavenger receptor of human monocyte-macrophages. We propose that intimal retention of Lp(a) by extracellular components of the atherosclerotic reaction places the lipoprotein in a microenvironment favoring subsequent peroxidative modification. The chronic production of lipid peroxide-modified Lp(a) together with unmitigated cellular clearance by scavenger receptors may contribute to the accumulation of lipoprotein-derived lipid in macrophage-derived foam cells of the atherosclerotic reaction.
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PMID:Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages. 153 81


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