摘要:

By using the euglycemic clamp technique and indirect calorimetry, we determined the degree of insulin resistance in 12 obese (body mass index >27.0 kg/m2), normotensive patients with type IIB hyperlipidemia (HLJIB) (total cholesterol &6.5 mmol/L and total triglycerides S2.0 mmol/L) and 17 control subjects (total cholesterol S6.1 mmol/L and total triglycerides <1.8 mmol/L) who were carefully matched for sex, age, and obesity. Fasting plasma insulin was higher in HLJIB patients than in control subjects (18.4±4.6 versus 8.9±1.2 mU/L, respectively; P=.O1O). The rates of whole-body glucose uptake were significantly lower in HLJIB patients than in control subjects during the last hour of the clamp (42.2 ±3.9 versus 54.6±2.8 /imol/kg per minute, respectively; P=.O13). Glucose oxidation during the last 30 minutes of the euglycemic clamp was lower in HLJIB patients than in control subjects (14.6±0.9 versus 19.0±13 fimo//kg per minute, respectively, />=.O17). Nonoxidative glucose disposal during the last 30 minutes of the euglycemic clamp was also lower in HLIIB patients than in control subjects, but the difference was not statistically significant (27.6±3_3 versus 35.8±2.8 /unol/kg per minute, respectively, P= M 9). Lipid oxidation during the clamp was completely suppressed in control subjects (-0.24±0.44 /tmol/kg per minute) but was significantly less suppressed in the HLIIB patients (0.94±0.29 jumol/kg per minute, P=.O24). Our study shows for the first time that obese patients with type IIB hyperlipidemia are insulin resistant and that this insulin resistance affects both oxidative and nonoxidative glucose metabolism.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

In the present study, the synthesis and secretion of transfected apolipoprotein (apo) A-IV was investigated in rat hepatoma McA-RH7777, a cell line that does not express apoA-IV raRNA or protein. An expression plasmid that contained the rat apoA-IV cDNA was transfected into the cells; five stable transformants were selected that harbor different copy numbers of the apo A-IV construct and secrete different amounts of apoA-IV. Gel filtration column chromatography and density gradient ultracentrifugation, combined with gel electrophoresis and electron microscopy techniques, demonstrated that (1) the secreted apoA-IV associated mainly with high-density lipoproteins (HDLs) and only a trace amount of apoA-IV was associated with very-low-density lipoproteins; (2) overexpression of apoA-IV resulted in an increased number of disk-shaped structures (thickness, =8.0 nm and diameter, =22 nm); and (3) the electrophoretic mobilities of the apoA-IV-containing particles differed from those of apoA-I-containing HDL. Expression of apoA-IV exerted no discernible effect on the density distribution or the secretion efficiency of apoB-100. Additionally, secretion of apoB-100 and apoA-IV exhibited opposite responses to serum: apoB-100 secretion was stimulated eightfold after addition of serum, whereas apoA-IV secretion was inhibited by 40%. These results suggest that synthesis of apoA-I V may lead to the formation of a subclass of HDL with a different metabolic fate than that of lipoproteins containing either apoA-I or apoB.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

This study examines the role of obesity and body fat distribution (ie, waist-to-hip ratio [WHR]) on cardiovascular disease (CVD) risk factors in 50 nondiabetic, obese (body mass index [BMI], 31±2 kg/m2, mean±SD), 45±10-year-old women. The data obtained at baseline and after weight loss were analyzed after dividing subjects by WHR into upper-body (WHR >0.80) and lower-body (WHR £0.80) groups and by median-split BMI into more obese (BMI s31) and less obese (BMI <31) groups. At baseline, the upper-body obese women, when compared with lower-body obese women, had higher plasma triglycerides (TGs) (175±85 versus 111±47 mg/dL, respectively;p<.00l) and lower high-density lipoprotein cholesterol (HDL-C) (44±10 versus 54±11, respectively,p<.01) but similar total and low-density lipoprotein cholesterol levels and blood pressure. There were no significant differences in these CVD risk factors at baseline by BMI split Although weight loss (-9±5 kg) lowered blood pressure and TGs irrespective of WHR or BMI, only upper-body obese women raised HDL-C. Moreover, the magnitude of the changes was greatest in women with an upper-body fat distribution. In women with WHR >0.80, HDL-C increased by 11%, to 49 mg/dL (p<.001), and TGs decreased by 24%, to 134 mg/dL (p<.001). The increase in HDL-C with weight loss was predicted in a linear model by the initial WHR, whereas the reductions in TGs and blood pressure were predicted by the change in body weight Thus, an upper-body fat distribution in women worsens the lipid risk factors for CVD posed by obesity, and weight loss is an effective intervention to improve lipid profiles in these women. Although weight loss improved CVD risk factors regardless of BMI or WHR, the magnitude of the increase in plasma HDL-C and decrease in TGs in women with an upper-body fat distribution suggests that weight loss in these women has the greatest potentiality of reducing their risk factors for CVD.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The apolipoprotein (apo) E4 polymorphism is associated with increased risk for symptomatic coronary artery disease (CAD). This study examines whether the apo«4 allele is associated with an increased risk for exercise-induced silent myocardial ischemia (SI) in healthy, older (62 ±7 years; mean±SD), normocholesterolemic, nonsmoking male volunteers. The apoe4 allele was present in 20 of 45 (44%) men with SI on graded exercise treadmill testing compared with 22 of 127 (17%) men of comparable age with normal exercise testsp><.001), resulting in a crude relative risk of 2.57 (95% confidence limits, 1-57 to 4.23) for SI in men with the apoe4 allele compared with those without theeXallele. Although the lipoprotein lipid levels did not differ between men with normal exercise tests and those with SI, the men with the apoE 4/3 phenotype had higher total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels than those with the apoE 2/3 and 3/3 phenotypes (p<.05). Men with SI and the apoE 4/3 phenotype were older (64±5 versus 57±8 years,p<.01) and leaner (p<.01) than the normal non-SI men with the apoE 4/3 phenotype. The older age of the men with SI and the apoE 4/3 phenotype is consistent with a progression of atherosclerosis over time. Men with SI and the apoE 3/3 phenotype were of comparable age and body composition to apoE 3/3 phenotype men with normal exercise tests. Thus, even in the presence of normal LDL-C levels, the apoe4 allele may predispose older men to SI.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Recent evidence has shown the presence ofChlamydia pneumoniaeantigens and nucleic acid in coronary artery atheromas from autopsy patients in South Africa. In this study, the immunocytochemical technique was used to demonstrateC pneumoniaeantigens in atheromas of the aorta in autopsy patients from retrospective aortic atherosclerosis studies at the University of Washington. Hie patients were 34 to 58 years old. Immunoperoxidase staining usingChlamydia-spetiRcmonoclonal antibodies showed one of four fatty streaks and six of 17 fibrous plaques were positive forC pneumoniaeantigens; four control aortic tissues were negative. Two of the positive plaques were from the same patient Double-label immunocy* tochemical staining usingChlamydia-and tissue type-specific monoclonal antibodies demonstrated the antigens in the cytoplasm of macrophages and smooth muscle cells in the atheromatous lesion. This study suggested a wider involvement ofCpneumoniaeorganisms in atherosclerotic lesions of the arterial system than has previously been documented.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The influence of different retinoids on apolipoprotein A-I (apoA-I) synthesis and secretion was investigated in primary monolayer cultures of hepatocytes from cynomolgus monkeys. Addition of retinol (vitamin A) and retinoic acid to the culture medium resulted in a timeand dose-dependent increase in the secretion of apoA-I. No effect was observed during the first 24 -hour incubation period; however, apoA-I secretion was enhanced 1.5 -fold in the following 24-hour period in the presence of 10 /tmol/L retinoic add. Maximal stimulation (2.7-fold) was obtained at 10 /unol/L retinoic acid during a third 24-hour incubation. In these experiments apoB-100 secretion was unaffected. When [3!S]methionine incorporation studies were performed de novo synthesis of apoA-I was increased, whereas total protein synthesis remained constant These observations indicated that the induction of apoA-I synthesis is not part of a general effect of retinoic acid on hepatic protein synthesis. Among different natural and synthetic retinoids, retinoic acid and its9-cisand 13-cw isomers were equally active and were the most potent inducers of apoA-I synthesis, whereas the maximal stimulation induced by retinol was lower (1.6-fold). ApoA-I mRNA abundance was increased threefold in hepatocytes exposed for 72 hours to 10 /unol/L retinoic add, which was assodated with a twofold increase in the transcriptional rate of the apoA-I gene. In contrast, no changes were found in the apoB-100 mRNA level and transcriptional activity of the apoB-100 gene. We conclude that retinoids enhance apoA-I synthesis in simian hepatocytes by transcriptional regulation.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We examined the effects of dietary n-3 polyunsaturated and saturated fatty acids on the development of the atherogenic process in mice and on the macrophage ability to secrete several effector molecules that may be involved in the atherogenic process. The secretion of inflammatory proteins such as tumor necrosis factor-* (TNF-<*) and interleukin-1/3 (IL-10) and the production of lipoprotein lipase (LPL), nitrogen oxide (NO2), and prostaglandin Ej (PGEJ were evaluated in peritoneal macrophages isolated from atherosclerosis-susceptible C57BIV6J mice. The mice were assigned at random to three experimental groups: the first group was fed a semi-defined control diet (control diet); the second group was maintained on the control diet supplemented with 10% menhaden oil (menhaden diet); and the third group received the control diet supplemented with 10% palm oil plus 2% cholesterol (saturated fat diet). Macrophages derived from mice fed the menhaden diet showed a suppression of their basal TNF-or mRNA expression and production. They also presented a dramatically decreased ability to express TNF-aand IL-10 raRNAs in response to exposure to lipopolysaccharide (LPS) compared with the macrophages from the control group. LPL mRNA and protein expression were downregulated after 6 and 15 weeks of menhaden-diet feeding. Significantly higher NO2production in response to interferon gamma was found, both after 6 and 15 weeks of diet feeding, in the menhaden group compared with the control group. In addition, prostaglandin production and macrophage tumoricidal activity in response to LPS were decreased in this group compared with the control group. Macrophages derived from the saturated fat group did not show any significant alterations in TNF-a, LPL, NO2, or PGE? secretion compared with controls. Interestingly, we observed a progressive increase of the LPS-induced IL-1/3 gene expression and secretion among macrophages harvested from mice receiving the dietary supplement of saturated fatty acids. At 6 and 15 weeks histologic examination of the atherosclerotic lesions did not reveal any important lesions in the control and menhaden groups, whereas a gradual development of fatty streaks was observed in the saturated fat group. After 15 weeks of diet, the addition of saturated fatty acids to the control and menhaden experimental diets for 10 additional weeks resulted in a major development of lesions in the control group, whereas only slight lesions were observed in the menhaden group. These data indicated a beneficial effect of dietary n-3 polyunsaturated fatty acids on the development of atherosclerosis and underlined possible involvement of cytokines in atherogenesis.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The mechanism(s) of inhibition of endothelium-dependent relaxation (EDR) by oxidized low-density lipoprotein (Ox-LDL) was examined in isolated porcine coronary arteries and rabbit aortas. Incubation with Ox-LDL but not native LDL caused the inhibition of thrombinor acetylcholine-induced EDR, whereas A23187-induced EDR was preserved after incubation with Ox-LDL, Lysophosphatidylcholine (lysoPC), which was abundant in Ox-LDL and was found to be transferred from Ox-LDL to endothelial cells, also caused the inhibition of EDR in response to thrombin or acetylcholine but not to A23187. Ox-LDL depleted of lysoPC, which was prepared by phospholipase B, failed to inhibit the vasorelaxation. Colncubatlon with staurosporine or calphostin C, potent inhibitors of protein kinase C, attenuated the EDR inhibition by Ox-LDL or lysoPC. Phorbol 12-myristate 13-acetate, a specific protein kinase C activator, caused the EDR inhibition, and its effect was attenuated by staurosporine or calphostin C. Furthermore, lysoPC was capable of activating protein kinase C purified from cultured porcine endothelial cells. In conclusion, protein kinase C activation plays a role in the inhibition of surface receptor-mediated EDR by Ox-LDL, and lysoPC transferred from Ox-LDL to endothelial cells may be involved in the activation of protein kinase C.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The most stringent dietary recommendations of the National Cholesterol Education Program (NCEP) are to limit fat intake to <30% of calories, saturated fat intake to <7% of calories, and cholesterol intake to <200 mg/d (Step 2 diet). There is debate as to whether the remaining fat in the diet should be relatively high in monounsaturated or poly unsaturated fatty acids. We examined this issue by testing the effects of diets meeting the aforementioned guidelines that were enriched in three different vegetable oils on plasma lipids in the fasting and postprandial states in a clinically relevant population. Female and male subjects (n=15, mean age, 61 years) with low-density lipoprotein cholesterol (LDL-C) concentrations >130 mg/dL were studied under strictly controlled conditions. Subjects were first placed on a diet similar to that currently consumed in the United States to stabilize plasma lipids with respect to identical fat and cholesterol intakes. The subjects then received diets meeting NCEP Step 2 criteria in which two thirds of the fat calories were given either as canola, corn, or olive oil in a randomized, double-blinded fashion for 32 days each. Plasma cholesterol concentrations declined after consumption of diets enriched in all the test oils; however, the declines were significantly greater for the canola (12%) and corn (13%) than for the olive (7%) oil-enriched diet Mean plasma LDL-C concentrations declined after consumption of diets enriched in all the test oils (16%, 17%, and 13% for canola, corn, and olive oil, respectively), and the magnitude of the declines was statistically indistinguishable among the test oils. Mean plasma high-density lipoprotein cholesterol (HDL-C) concentrations declined after consumption of the baseline diet, and these declines were significant for the canola (7%) and corn (9%) oil-enriched diets. Changes in LDL apolipoprotein (apo)B concentrations paralleled those of LDL-C. Switching from the baseline to the vegetable oil-enriched diets had no significant effect on plasma triglyceride, apoA-I, and lipoprotein(a) concentrations or the total cholesterol to HDL-C ratio. LDL apoB to apoA-I ratios were significantly reduced when the subjects consumed the vegetable oil-enriched diets. Differences similar to those observed in the fasting state were observed in the postprandial state. The major finding of this study is that significant reductions in LDL-C and apoB levels can be achieved in middle-aged and elderly women and men with initial LDL-C levels > 130 mg/dL by reducing dietary saturated fat and cholesterol intake and by incorporating vegetable oils rich in either monounsaturated fatty acids (canola and olive oil) or polyunsaturated fatty acids (corn oil) as part of an NCEP Step 2 diet Although differential effects were seen after the consumption of the three different oil-enriched diets in some plasma lipid measures, none of these oils had a significant advantage in terms of altering the overall lipoprotein profile.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We have previously shown that high-frequency, high-resolution ultrasound can characterize the acoustic properties and composition of fatty plaques in cholesterol-fed rabbits. To determine whether quantitative ultrasound can delineate the regression of atherosclerotic lesions by detecting a change in their composition from fatty to fibrous types induced by alterations in dietary regimen, we fed six New Zealand White rabbits a 2% cholesterol diet for 3 months, followed by a standard diet for 3 additional months to promote the development of fibrous intlmal lesions. Segments of aortas were excised, and backscattered radiofrequency data were acquired from 400 to 600 independent sites in each specimen with an acoustic microscope operated at 50 MHz. Control data were provided by measuring backscatter from adjacent portions of the aortas devoid of lesions. Histological and immunocytochemical analyses of the fibrous intimal lesions confirmed the presence of smooth muscle cells and abundant connective tissue with little appreciable lipid. Backscatter from normal aortic segments (&#151;30.7±1.0 dB) was approximately 10-fold greater than that from fibrous lesions (-42.4±1.0 dB;p<.05). We previously reported that integrated backscatter from fatty lesions was -50.6±0.7 dB, or approximately 10-fold less than that from fibrous lesions (p<.05). Values for integrated backscatter from the media of each tissue type were approximately equal (&#151;30.0±1.7 versus &#151;30.7±1.6 versus &#151; 33.4±0.8 dB for normal versus fibrous versus fatty tissues, respectively;P=notsignificant). Thus, quantitative ultrasonic tissue characterization sensitively differentiates between fibrous and fatty atherosclerotic plaque and normal tissue in the presence of experimental diet-induced atherosclerosis. These results suggest that alterations in dietary regimens may elicit changes in the composition of vascular plaques that are detectable with quantitative ultrasound.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID