摘要:

Abstract We studied whether serum basic proteins (BPs) produce abnormal changes in the mass of cellular lipids in fibroblasts from patients with hyperapobetalipoproteinemia (hyperapoB) and if inhibition or stimulation of protein kinase C affects these processes. In normal cells, BP I increased the mean mass of triglycerides about twofold, whereas there was significantly less stimulation in hyperapoB cells (P<.005). The increase in the mass of cell cholesteryl esters seen in normal cells with BP I was also significantly reduced in hyperapoB cells (P<.005). In contrast, BP II abnormally stimulated the mass of cell cholesteryl esters sixfold in hyperapoB cells (P<.005). BP I also stimulated the mass of total phospholipids about twofold in normal cells, an effect that was reduced by about one third in hyperapoB cells (P=.08). No abnormality was found in hyperapoB cells with BP III. H-7, an inhibitor of protein kinase C, decreased the effects of BP I and BP II in normal and hyperapoB cells. C:8, an analogue of diacylglycerol, activated protein kinase C and stimulated triglyceride formation in normal (fourfold) and hyperapoB (fivefold) cells in the absence of BP I. When added with C:8, BP I further increased triglyceride production 1.5-fold in normal cells but not in hyperapoB cells. Two cellular abnormalities in lipid metabolism in hyperapoB fibroblasts were found, one with BP I, another with BP II. Protein kinase C activity was not deficient in hyperapoB cells, and the defect(s) may occur at another, perhaps earlier, step in the pathway.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Cytokines, important biochemical mediators of inflammation, cause a rapid fall in the plasma concentration of cholesterol in vivo. One mechanism by which cytokines may cause acquired hypocholesterolemia is by decreasing the hepatic synthesis and secretion of apolipoproteins. To test this hypothesis, we incubated Hep G2 cells with human recombinant tumor necrosis factor-α, interleukin-1β, and interleukin- 6. Each of the cytokines resulted in a dose-related reduction in the concentrations of apolipoprotein (apo) A-I, apoB, and lecithin:cholesterol acyltransferase (LCAT) activity in the medium after 24 hours of incubation. The effect of cytokines on apolipoprotein accumulation was not affected by preincubation of Hep G2 cells with fatty acids. Cytokines decreased the concentration of cellular apoA-I mRNA in a dose-related fashion but did not affect cellular concentrations of apoB mRNA. The concentrations of triglyceride and cholesterol were also reduced in the medium of cells incubated with cytokines. Total cell sterol synthesis rates were calculated by [14C]acetate incorporation. Cells incubated with interleukin-6 had a 31% increase in sterol synthesis rate but a 41% decrease in sterol secretion. These data suggest that these cytokines can decrease the hepatic synthesis and/or secretion of apolipoproteins and that this may explain, in part, the acquired hypocholesterolemia seen during acute and chronic inflammation.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Little is known about the relation between serum sex hormones and either coronary heart disease or the development of atherosclerosis in women. We measured serum estrone concentrations in 87 postmenopausal women (age, 50 to 81 years) who were admitted for diagnostic cardiac catheterization. None of the women were on estrogen replacement therapy. Cases (n=62) were defined as those women who had >1 coronary artery with a50% occlusion. All control subjects (n=25) had 0% to 24% occlusion of all coronary arteries. Estrone concentrations, as measured by a combination of extraction, column chromatography, and radioimmunoassay, showed little difference between cases and control subjects. A difference of 6 pg/mL in the estrone level was not associated with a significantly increased risk of coronary artery disease (odds ratio [OR], 1.85; 95% confidence intervals [CI], 0.60, 5.2). Examination of mean estrone levels on the basis of the number of occluded vessels was also not significant. The primary predictors of coronary artery disease in this population were a history of diabetes (OR, 8.8; CI, 1.5, 51.4) and age (5-year increments; OR, 2.1; CI, 1.2, 3.8). There was also some suggestion that women who reported higher lifetime physical activity levels were at a reduced risk for developing coronary artery disease (OR, 0.18; CI, 0.05, 0.65). These preliminary results do not support the hypothesis that serum estrogens are related to coronary artery disease in older women, but these findings need to be replicated in larger populations of older women. (Arterioscler Thromb. 1994;14:14-18.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Sex hormones may play a role in the determination of cardiovascular disease. Recently lipoprotein(a) (Lp[a]) has been recognized as a risk factor for coronary heart disease. Estrogens and anabolic steroids have been reported to alter Lp(a) levels, yet no data are available on the association between in vivo concentrations of sex hormones and Lp(a) concentrations. We examined the possible associations of sex hormone-binding globulin, total and free testosterone, estradiol, and dehydroepiandrosterone sulfate to Lp(a) concentrations in men in two population-based studies (San Antonio Heart Study [n=178] and a Finnish study on the association between insulin resistance and atherosclerosis [n=87]). In neither study were sex hormones significantly related to Lp(a) concentrations. In addition, Lp(a) was significantly related to apolipoprotein(a) molecular weight (which was measured in the Finnish study only). These results were unchanged when Lp(a) concentrations were adjusted for apolipoprotein(a) molecular weight (a strong correlate of Lp[a] concentrations). We conclude that in vivo concentrations of sex hormones are unlikely to be associated with Lp(a) concentrations in men.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract The formation of an endothelial cell lining on the inner surface of polymeric grafts may reduce the inherent thrombogenicity of synthetic implants. Endothelial cell transplantation onto the luminal surface of grafts has been suggested as one method of creating new endothelial cell linings on grafts. The purpose of this study was to morphologically evaluate the very early events of healing (between 4 and 14 days) of 1-mm-internal-diameter expanded polytetrafluoroethylene (ePTFE) grafts that were treated with autologous microvessel endothelial cells at the time of graft implantation. We evaluated the development of new intimal linings in microvascular endothelial cell-sodded 1-mm ePTFE vascular grafts and compared their healing characteristics with noncell- treated grafts by using a rat aortic graft model. Endothelial cells were isolated from intraperitoneal fat pads of female rats and transplanted onto the grafts by using a pressure sodding method. One-centimeter-long grafts were immediately implanted as interpositional grafts in the aorta. Non-celltreated grafts were also implanted. Grafts were explanted 4, 7, and 14 days after implantation and were evaluated by light and scanning electron microscopy. Morphometric analysis of the graft surfaces revealed the cellular coverage in sodded grafts to be 93.7±8.7% and in nonsodded grafts, 1.1±1.9%. Areas not covered by cells exhibited thrombus and bare graft. The luminal lining of cells exhibited morphological characteristics, indicating they were antithrombogenic, based on morphological criteria, and exhibited characteristics of endothelium. We conclude that microvascular endothelial cell sodding of microvascular ePTFE grafts results in a dramatic acceleration of the formation of a luminal cell lining that covers more than 90% of the luminal surface of grafts by 7 days. While control grafts exhibited a thrombogenic surface, sodded grafts exhibited an antithrombogenic cell lining, as indicated by the absence of adherent platelets, white cells, and fibrin.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Atherosclerotic lesions contain relatively large quantities of IgG. We have previously shown that both human and rabbit sera contain autoantibodies against epitopes of oxidized (Ox) low-density lipoprotein (LDL) and that LDL isolated from atherosclerotic lesions contains small amounts of tightly bound IgG. However, it is not known whether IgG isolated from atherosclerotic lesions recognizes epitopes present in native LDL or Ox-LDL. IgG was isolated from Watanabe heritable hyperlipidemic (WHHL) rabbit atherosclerotic lesions by sequential salt extractions, purified by fast protein liquid chromatography on protein G, and used in a solid-phase radioimmunoassay. IgG and immune complexes were also isolated from the saline extracts of human lesions by adsorption onto latex beads coated with anti-human IgG antibodies or protein A. IgG isolated from rabbit lesions showed significant titers against malondialdehyde (MDA)-modified LDL and LDL oxidized by copper ions for 4 and 18 hours but not against native LDL. On Western blots, lesion IgG stained MDA-LDL and fragments of Ox-LDL. Western blots of immune complexes isolated from human lesions revealed the presence in the isolated complexes of both apoprotein B and apoprotein B fragments, which reacted with antibodies to MDA-lysine. Furthermore, rabbit lesion IgG immunostained epitopes of Ox-LDL present in human atherosclerotic lesions. Immunostains obtained with rabbit lesion IgG were similar to those obtained with a monoclonal antibody specific for MDAlysine. The results show that human and rabbit atherosclerotic lesions contain IgG that recognizes epitopes characteristic of Ox-LDL. These data suggest that immunologic processes may be an important component of the atherogenic process.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Because previous studies show that lipoproteins affect platelet aggregation, we studied the effect of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) on the binding of fibrinogen, which mediates platelet-platelet contact. Neither LDL nor HDL induced125I-fibrinogen binding at concentrations up to 2 g protein/L. In contrast, platelets stimulated with 10 μmol/L ADP bound 63 734±2453 molecules of fibrinogen per platelet. A 5-minute preincubation with LDL (0.5 to 2 g/L protein) induced a dose-dependent increase to 91 3O7±2164 molecules of fibrinogen per platelet at 1.5 g/L, which is in the range found after optimal stimulation with a-thrombin. The increased fibrinogen binding in the presence of LDL resulted in faster aggregation with a 16% increase in single platelet disappearance and a faster optical aggregation at 5 μmol/L ADP and 1.5 g protein/L LDL. Inhibition of prostaglandin G2/H2-thromboxane A2formation with indomethacin (30 μmol/L) did not change the stimulation by LDL. In contrast, modification of h/sine residues of LDL, which is known to prevent specific binding to platelets, completely abolished the effect of LDL. Under the same conditions HDL did not change fibrinogen binding or aggregation. LDL also enhanced α-thrombin-induced [12514C]serotonin secretion, but this property was not affected by h/sine modification of LDL. These data indicate that LDL enhances platelet aggregation by stimulating the mechanisms that control exposure of fibrinogen binding sites on the gh/coprotein IIB/IIIA complex via a mechanism that differs from the effect of LDL on secretion.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract T lymphocytes, macrophages, and oxidized lowdensity lipoprotein (Ox-LDL) are collocalized in early atherosclerotic lesions. Using a low-endotoxin in vitro system, we observed that Ox-LDL but not native LDL induced the production, by both freshly adherent human peripheral blood monocytes and human monocytic THP-1 cells, of the α chemokine interleukin (IL)-8, a potent chemoattractant for T lymphocytes. Marked IL-8 induction by Ox-LDL did not require IL-1β generation in THP-1 cells. Ox-LDL-induced chemokine production was selective, as Ox-LDL did not stimulate the production by THP-1 cells of the T-lymphocyte chemotactic β chemokine macrophage inflammatory protein (MlP)-la. IL-8 induction increased in proportion to the extent of oxidation of LDL as measured by the content of lipid oxidation end products.To identify potentially active components of Ox-LDL, we tested malondialdehyde, an arachidonate- derived lipid oxidation product, and 9-hydroxyoctadecadienoic acid, an oxidation product of linoleate, the major polyunsaturated fatty acid in LDL, and observed that they Induced IL-8 generation in the absence of Ox-LDL. Furthermore, when most free lipid oxidation products were removed from Ox-LDL by dialysis, some IL-8-inducing activity was released into the dialysate. However, the major IL-8-inducing activity was not dialyzable. To address the nature of the LDL particle modification required to induce IL-8, acetylated or malondialdehyde-trcated native LDL particles were monitored for activity. Neither procedure rendered LDL capable of inducing IL-8. However, phospholipase A$-treated LDL induced THP-1 cell expression of IL-8. Thus, Ox-LDL induced a chemokine in monocytic THP-1 cells by a mechanism that did not absolutely require IL-1/3, appeared to be predominantly mediated by particle-associated and nondiffusible end products of lipid degradation, and could be reproduced by phospholipase A2 treatment of LDL.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Coronary thrombosis is regarded as the final occlusive event in the progress of coronary heart disease (CHD). Disturbances of the hemostatic system may favor this process and thus may indicate increased risk of myocardial infarction. Coagulation and lipid factors were measured in 2116 healthy male participants of the Prospective Cardiovascular Miinster (PROCAM) study. After 6 years of follow-up, 82 coronary events (9 sudden cardiac deaths and 14 fatal and 59 nonfatal myocardial infarctions) were observed. The mean plasma fibrinogen levels of the event and nonevent groups differed by 0.25 g/L (2.88 [SD, 0.68] versus 2.63 [SD, 0.63] g/L, respectively; P=.001). The incidence of coronary events in the upper tertile of the plasma fibrinogen distribution was 2.4-fold higher than in the lower tertile. By multiple logistic function analysis, plasma fibrinogen was found to be an independent risk indicator for CHD (P<.05). Individuals in the high serum low-density lipoprotein (LDL) cholesterol tertile who also showed high plasma fibrinogen concentrations had a 6.1-fold increase in coronary risk. Unexpectedly, individuals with low plasma fibrinogen had a low incidence of coronary events even when serum LDL cholesterol was high. The mean factor VIIc activities in the event and nonevent groups did not differ significantly (112.3% [SD, 19.9] versus 108.4% [SD, 21.6]; P=.09). There was, however, a trend toward higher factor VIIc values when only fatal events were taken into account. Thus, higher levels of plasma fibrinogen markedly increased the predictive power of high serum LDL cholesterol. Low plasma fibrinogen is associated with low coronary risk even when LDL is raised.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Abstract Dietary studies have established a connection between plasma lipoproteins and coagulation factor VII. The present study was undertaken to specifically examine whether factor VH is activated during alimentary lipemia and to investigate the relations of factor VII mass and activity state with fasting and postprandial lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore determined in plasma samples taken before and after intake of a standardized, oral fat load of a mixed-meal type in 33 men (mean age±SD,48.8±3.2 years) with a previous myocardial infarction at a young age and 10 healthy, age-matched control subjects. A panel of methods for factor VII determination was used to ensure that changes in all potentially existing forms of the factor during alimentary lipemia would be included. Substantial activation of factor VII was found to occur during alimentary lipemia, whereas the number of factor VII molecules remained constant or even appeared to decrease after the test meal. Activation of factor VH was more pronounced in control subjects than patients, and the proportion of activated factor VII molecules was higher in control subjects. Interestingly, factor VII activation, which correlated quantitatively with the degree of postprandial triglvceridemia, seemed to be related to FFA production during lipolysis of triglyceride-rich lipoproteins that were generated in response to fat intake. Postheparin plasma lipoprotein lipase activity was lower in patients, which could offer one explanation why factor VII activity was lower during alimentary lipemia in these subjects despite their exaggerated postprandial triglyceridemia. Thus, activation of coagulation factor VII during alimentary lipemia may result in a procoagulant state that is likely to promote the formation of a coronary thrombus in individuals with established coronary artery disease.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID