摘要:

Prospective epidemiological studies found that the plasma level of factor VII activity was a risk factor for ischemic heart disease (LHD). Our laboratory previously demonstrated that young adults (mean age, 35 years) at high risk of IHD had significantly higher plasma factor VII activity and antigen levels than did comparable young adults at low risk. To study the relation of factor VIT with lipid metabolism in even younger adults (<30 years), using standard techniques we measured plasma factor VII activity and antigen, plasma fibrinogen, and fasting serum lipid fractions in healthy male and female subjects who were at low risk of IHD and who were not on medication. Factor VII antigen correlated significantly with total serum cholesterol, fasting serum triglycerides, and high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol (p<0.01), and factor VII activity correlated with total and HDL cholesterol (p<0.05) in the men (n=132); however, fibrinogen level did not correlate significantly with any lipid level in this group. We found no significant correlation of factor VII activity or antigen with any lipid levels in the women (n=65). Our data support the hypothesis that control of plasma factor VII level is linked to lipid metabolism in normal physiology in men. Thus, factor VII level may reflect the mechanism by which male gender imparts added risk for IHD, independent of other established risk factors. This study also supports the use of the factor VH antigen assay, a highly reproducible method, in studies of the relation of factor VH to the risk of IHD.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This study compares the effects of glucose and fatty acid on hepatic lipid synthesis and apolipoproteln (apo) B secretion. To do so, varying concentrations of either glucose or oleic acid were added to the medium in which HepG2 cells were being incubated. Intracellular triacylglycerol and cholesteryl ester synthesis and secretion were measured by addition of radioisotopic tracers and by determination of mass, whereas apo B concentration in the medium was measured by a specific enzyme-linked immunosorbent assay. The data indicate that increasing concentrations of glucose in the medium resulted in increased synthesis of triacylglycerol within the cell and increased secretion of triacylglycerol into the medium. Apo B secretion into the medium, however, did not change, and intracellular synthesis and secretion of cholesteryl ester did not change as well. By contrast, addition of oleic acid to the medium resulted in increased synthesis and secretion of both cholesteryl ester and triacylglycerol, and this was associated with increased secretion of apo B into the medium. Thus, a carbohydrate load resulted in secretion of normal numbers of triacylgtycerol-enriched apo B particles by this hepatocyte cell line, whereas a fatty acid load led to the secretion of increased numbers of apo B particles, which were essentially normal in composition.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Atherogenesls is associated with alterations in the properties of different cell types, including monocytes/ macrophages (foam cell formation), platelets (increased aggregation), endothelial cells (injury), and smooth muscle cells (SMCs) (lipid accumulation or foam cell formation). Oxidized low density lipoproteins (ox-LDL) play a key role in this vascular pathology. This study investigated the ability of ox-LDL to elicit chemical signaling events in cultured human vascular smooth muscle cells (VSMCs). Ox-LDL was found to stimulate phospholipase C-mediated phosphoinositide turnover in human VSMCs. This response occurred rapidly (within 1 minute) and at low concentrations of ox-LDL (half-maximal effective concentration, ≈5 /tg/ml). Qx-LDL—stimulated inositol phosphate accumulation in human VSMCs was inhibited by pretreatment of cells with phorbol 12-myristate 13-acetate and with compounds that elevate cyclic AMP or cyclic GMP. Ca2+ antagonists also blocked the effects of ox-LDL on phosphoinositide turnover. Inhibitors of receptor-endocytotic processes (including receptor clustering, cross-linking, and cytoskeleton-dependent internalization) effectively prevented ox-LDL-induced inositol phosphate generation. The data suggest that ox-LDL promotes phospholipase C-mediated phosphoinositide turnover in a manner analogous to that for other Ca1±mobilizing hormones. The results also support an association between phosphoinositide turnover and receptor-mediated endocytosis. Prevention of the direct effects of ox-LDL on SMCs could prove an interesting therapeutic avenue for the prevention of atherosclerosis.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The influence of different fibrates on apolipoprotein metabolism was investigated. Administration of fenoflbrate provoked a dose-dependent decrease in plasma cholesterol concentration that was already evident after 1 day. Intestinal apolipoprotein (apo) A-I and apo A-IV mRNA levels remained fairly constant In contrast, liver apo A-I, apo A-II, and apo A-IV mRNA levels decreased in a dose-dependent fashion, which was associated with a lower transcription rate of the apo A-I bat not the apo A-II gene. The decline in hepatic apo A-I, apo A-II, and apo A-IV mRNA had already started after 1 day and was associated with a drop in plasma apo A-I and apo A-IV concentrations. Plasma apo E had already decreased after 1 day of fenofibrate, whereas apo B initially remained constant and increased only after 14 days of fenofibrate at the highest dose. Hepatic and intestinal apo B mRNA contents and liver, heart, kidney, and testls apo E mRNA contents were only marginally affected after treatment with fenofibrate. liver low density lipoprotein receptor mRNA levels rose slightly after a 3-day administration of the highest dose of fenofibrate. Both clofibrate and gemfibrozil had effects comparable to those of fenofibrate on liver and intestinal apolipoprotein mRNA levels except for liver apo A-II mRNA, which decreased only marginally. Compared with fenofibrate, clofibrate caused similar changes in plasma cholesterol, apo A-I, apo A-IV, and apo E concentrations, whereas gemfibrozil increased plasma cholesterol and apo E without changing apo A-I and apo A-IV concentrations. In conclusion, all fibrates influence the expression of the apo A-I, apo A-II, and apo A-IV genes but not the apo B and apo E genes in a tissue-selective manner. After clofibrate and fenofibrate but not after gemfibrozil, these alterations are reflected by similar changes in plasma apolipoprotein concentrations.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Enzymatic activity and raRNA abundance for neutral bile salt-dependent cholesteryl ester hydrolase (CEH) were determined in rat and rabbit tissues. In rat liver and intestine, enzyme activity and mRNA levels varied independently. Particularly striking in most tissue samples was the absence of detectable CEH mRNA in the presence of enzymatic activity, suggesting that there was an exogenous source of enzyme. Rabbits differed from rats in four ways. First, neither CEH activity nor mRNA was present in any liver sample. Second, CEH mRNA was present in nearly all intestinal samples, and its abundance tended to correlate with enzymatic activity. Third, rabbit CEH mRNA was approximately 250 bases shorter than the rat message. Fourth, we have previously shown that rat plasma contains CEH activity, whereas in the present studies, rabbit plasma did not contain such activity. Overall, our studies indicate that CEH activity in rat liver, intestine, and plasma can be derived exogenously, most likely from the uptake and transport of pancreatic enzyme. In contrast, in rabbit the lack of CEH activity in plasma and liver and the capacity of the intestine for in situ synthesis of CEH suggest that this animal does not have the same ability to distribute pancreatic CEH. These species differences in CEH metabolism may partly explain the greater susceptibility of rabbit tissues to accumulate cholesteryl esters.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The distribution of Lp(a) lipoprotein (Lp[a]) and genetic apolipoprotein(a) (apo[a]) isoforms in plasma samples from 29 healthy normolipidemic subjects of known apo(a) phenotype was evaluated by density gradient ultracentrifugation. The density of Lp(a) was directly related to the size of the apo(a) isofonn, ranging from 1.043 g/ml for the LpF phenotype to 1.114 g/ml for the LpS4 phenotype. Heterozygotes had two distinct Lp(a) particles, each containing one of the respective isofonns in plasma. In each heterozygote, the concentration of the lighter Lp(a) species was higher than that of the denser Lp(a) population. These data suggest that apo(a) alleles determine the density and the metabolism and thereby also the concentrations of Lp(a) particles in plasma.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Repair and remodeling processes initiated by arterial injury are thought to be critical in the pathogenesis of important vascular disorders. However, how these processes are related to specific types of injury is not well defined. Consequently, we compared arterial responses to several types of injury. Segments of rabbit carotid arteries were injured by Intraluminal passage of an inflated embolectomy catheter, by hyperdistending the arteries with sterile saline, or by flushing them briefly with Triton X-100. Ballooning and Triton treatment removed the endothelium while imposing hyperdistending or nonhyperdistending injury on the vessel media. Hyperdistension with sterile saline caused medial injury but only transient and focal endothelial denudation. All modes of injury caused medial damage that was repaired within 2-7 days as assessed by vessel wall DNA content and synthesis and by capacity to contract In addition, ballooned arteries recovered their capacity to exhibit diameter reductions induced by decreased blood flow once the endothelium had regenerated. The two injuries that caused endothelial denudation, ballooning and Triton treatment, resulted in equal intimal thickening after 6 weeks despite lower shortand long-term rates of cell replication after Triton-induced Injury. Only ballooning resulted in chronic turnover of intimal smooth muscle cells after injury. No neointimal proliferation followed hyperdistension with saline despite significant medial injury. These latter findings suggest that even severe medial injury does not lead to intimal proliferation in the absence of endothelial denudation.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To determine whether probucol's ability to confer antioxidant protection to low density lipoprotein (LDL) could be dissociated from its ability to lower high density lipoprotein (HDL) cholesterol, 17 hypercholesterolemic patients were treated with either a standard dose, 1 g/day (4 tablets), or a low dose, 250 mg/day (1 tablet), of probucol for a 6-month period. Effects of therapy on lipoprotein levels and on susceptibility of LDL to in vitro oxidation were measured at frequent intervals. Probucol levels in plasma LDL rose less rapidly in the 1-tablet group but were nearly 50% of levels in the 4-tablet group after 6 months. HDL cholesterol and apolipoprotein A-l decreased 17.6% and 27.9%, respectively, in the 1-tablet group compared with 28.0% and 383%, respectively, in the 4-tablet group (p=0.07 and p=0.06). In the 4-tablet group, LDL was protected from copper and endothelial cell-mediated oxidation after 2 months of therapy. In the 1-tablet group, equal degrees of protection occurred, but only after 6 months of therapy. In the whole study group, the decrease in LDL susceptibility to copper or endothelial cell-mediated oxidative modification was correlated with the content of probucol in LDL (r=0.73, r=0.65,p<0.005). Additionally, the decrease in HDL cholesterol level was correlated with the increase in protection to LDL from oxidative modification (r=0.67 for copper, r=0.58 for endothelial cells,p< 0.05 for both) and also with the content of probucol in LDL (r=0.6, p=0.01). In conclusion, a low dose of probucol provides impressive protection to LDL against in vitro oxidation and modification, with less marked HDL cholesterol lowering. However, these effects are not completely dissociated from each other, and in fact, the extent of HDL cholesterol lowering was correlated with the LDL probucol content and the resulting antioxidant protection.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The antiatherogenic properties of high density lipoproteins (HDLs) are thought to reside in their involvement hi the reverse cholesterol transport pathway. Specific HDL-binding proteins could play a key role in this process. Two HDL-binding proteins of approximately SKI and 180 kd were identified in porcine liver by ligand blotting and were purified to apparent homogeneity by a combination of protein extraction, DEAE-cellulose chromatography, Con A-Sepharose chromatography, and preparative sodium dodecyl sulfate-polyacryiamide gel electrophoresis. Binding ofIZ5I-HDL by these proteins could be actively competed for by unlabeled HDL but not by low density lipoprotein. Polyclonal antisera have been raised against these two proteins. Each antiserum recognized only one of the HDL-binding proteins, indicating that they are not immunologically related. Moreover, striking differences in localization were observed in Immunohistochemical studies. The 90-kd protein is located within the hepatocellular plates, while the 180-kd protein is present along the lining of the sinusoids. These results suggest functional differences between the two HDL-binding proteins described.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We examined the relations of gender and lipoproteins to subclasses of high density lipoproteins (HDLs) in a cross-sectional sample of moderately overweight men (n=116) and women (n=78). The absorbance of protein-stained polyacrylamide gradient gels was osed as an index of mass concentrations of HDL at intervals of 0.01 nm across the entire HDL particle size range (7.2-12 am). At least five HDL subclasses have been identified by their particle sizes: HDL3c(7.2-7.8 nm), HDL3b(7.8-8.2 nm), HDL3a(8.2-8.8 nm), HDL2a(8.8-9.7 nm), and HDL2b(9.7-12 nm). Men had significantly higher HDL3band significantly lower HDL2aand HDL2bthan did women. Correlations of HDL subclasses with concentrations of other lipoprotein variables were generally as strong for gradient gel electrophoresis as for analytical ultracentrifugation measurements of HDL particle distributions. In both sexes, high levels of HDL3bwere associated with coronary heart disease risk factors, including high concentrations of triglycerides, apolipoprotein B, small low density lipoproteins, intermediate density lipoproteins, and very low density lipoproteins and low concentrations of HDL2cholesterol and HDL2mass. Plasma concentrations of HDL3cholesterol were unrelated to protein-stained HDL3blevels. HDL3cholesterol concentrations also did not exhibit the sex difference or the relations with lipoprotein concentrations that characterized HDL3b. Thus, low HDL3blevels may contribute in part to the low heart disease risk in men and women who have high HDL cholesterol. Measurements of HDL3cholesterol may not identify clinically important relations involving HDL3b.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID