摘要:

Intravascular ultrasound may be useful for studying the natural history of atherosclerotic lesions of different morphologies and for guiding interventional strategies. This study was designed to test the hypothesis that tissue appearance by intravascular ultrasound is related to the biomechanical properties of atheroma components. Forty-three atheroma caps were obtained from the abdominal aortas of 22 patients at autopsy and studied with an ultrasensitive, servo-controlled spectrometer. By measuring the static strain caused by increasing levels of compressive stress from 30 to 90 mm Hg, the uniaxial unconfined compression stiffness (ratio of stress to strain) was determined. After mechanical testing, specimens were imaged with a 6F, 20-MHz intravascular ultrasound transducer, and images were interpreted by an investigator who was unaware of the mechanical measurements. Specimens were classified as nonfibrous (n = 14), fibrous (n=18), or calcified (n=ll) based on intravascular ultrasound appearance. The static stiffnesses of the nonfibrous, fibrous, and calcified ultrasound classes were 41.2±18.8 kPa, 81.7±33.2 kPa, and 354.5±245.4 kPa, respectivelyp=0.0002 by analysis of variance). The times to reach static equilibrium (creep time) for the nonfibrous, fibrous, and calcified classes were 79.6±26.5 minutes, 50.2±20.0 minutes, and 19.4±8.1 minutes, respectivelyp=0.0007). Intravascular ultrasound appearance was most significantly related to biomechanical behavior when calcium deposits were noted; the differences in biomechanical behavior between nonfibrous and fibrous tissue appearances were less apparent Important biomechanical behavior of human atherosclerotic tissue can be predicted by intravascular ultrasound imaging; this technology may allow a detailed in vivo assessment of the stress-strain relation in diseased human arteries.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To compare the atherogenic potential of low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) under conditions where plasma levels of these lipoproteins are elevated, the influx of cholesterol in these lipoproteins into the aortic intima was measured in vivo in genetically hyperlipidemic rabbits from the St. Thomas's Hospital strain, an animal model that shares many of the features of the human disorder familial combined hyperlipidemia. Univariate linear regression showed that the arterial influx of LDL cholesterol (n=25), IDL cholesterol (n = 14), and VLDL cholesterol (n=10) was positively and linearly associated with plasma concentrations of LDL cholesterol in the range 0.2-6.4 mmol/1, of IDL cholesterol in the range 0.1-7.0 mmol/1, and of VLDL cholesterol in the range 0.7-8.5 mmol/1, respectively, and also with the extent of lesions in the arterial intima in the range 0-100% of the surface area. Multiple linear regression suggested that the arterial influx of LDL, IDL, and VLDL cholesterol was linearly dependent on plasma concentration, independent of lesion size. Furthermore, it appeared that the arterial influx of the three lipoproteins was linearly dependent on the extent of the lesions, independent of lipoprotein concentration. When influx was normalized for plasma concentration (intimal clearance) and for lesion size (compared within the same aorta), the intimal clearance of the larger IDL and VLDL particles was 15-35% less than that of the smaller LDL particles. These findings suggest that the quantitatively most important mechanism for transfer of plasma lipoproteins into the arterial intima involves nonspecific molecular sieving and that at elevated plasma levels, IDL and VLDL share with LDL the potential for causing atherosclerosis.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A relation between elevated triglyceride (TG) levels and alterations of the fibrinolytic system has been recognized in studies of patients with coronary heart disease. In this investigation, the total fibrinolytic activity and the levels of specific components of the fibrinolytic system were evaluated in plasma samples from a highly selected group of patients with type IV hyperlipoproteinemia before and after a dietary treatment aimed at reducing TG levels. The fibrinolytic response of type IV patients was comparable to that of normolipidemic subjects, whereas tissue-type plasminogen activator antigen levels before and after venous occlusionp<0.01) and resting plasminogen activator inhibitor-1 (PAI-1) antigenp><0.01) and activity (p<0.01) were significantly higher in hypertriglyceridemic subjects compared with controls. After dietary treatment, a 22% reduction in TG levels was attained in type IV patients, with no appreciable modification of fibrinolytic parameters. The analysis of the single-patient data revealed a tendency toward normalization of PAI-1 levels only in those patients who showed a TG reduction £20%. Very low density lipoproteins (VLDLs) from both normal and type IV patients concentration-dependently stimulated PAI-1 release by endothelial cells and HepG2 cells, with the effect of VLDL from type IV patients being more pronounced on HepG2 cells. The release of PAI-1 induced by VLDL in competent cells may thus account for the elevated levels of this antifibrinolytic protein that occur in hypertriglyceridemic patients.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Significant differences among individuals occur in the lipoprotein response to atherogenic diets in cynomolgus and African green monkeys. The range of concentrations of total plasma cholesterol (TPC) was 100-600 mg/dl and of apolipoprotein (apo) E (quantified by enzymelinked immunosorbent assay) was 3-20 mg/dl in the animal groups of this study. The correlation between the concentrations of TPC and of apo E was r=0.89 in these animals. To determine which lipoprotein classes contained the majority of apo E, agarose gel-filtration chromatography was used to subfractionate whole plasma. In hypercholesterolemic monkeys, the majority of the apo E and apo B-100 coeluted within the region of low density lipoprotein (LDL). In normocholesterolemic monkeys, the majority of apo E coeluted with apo A-I and high density lipoproteins. A strong positive correlation was seen between the concentrations of plasma apo E and LDL cholesterol (r=0.9), but there was no significant correlation between high density lipoprotein apo E and either TPC or plasma apo E concentrations. A positive correlation of r=0.8 was found between the LDL apo E to apo B-100 molar ratio and the average LDL particle size, suggesting an increase in the number of apo E molecules on the larger LDL particles. Within individual animals, LDL were heterogeneous and the LDL subtractions of lower density (1.02<d< 1.03 g/ml) had the highest proportion of apo E, although apo E was present on LDL of all densities. A strong positive correlation between plasma apo E concentration and coronary artery atherosclerosis was identified, and in stepwise regression analysis, plasma apo B concentration and the apo E to apo B molar ratio of LDL together accounted for more than 90% of the variation in the atherosclerosis end point of coronary artery intimal area. These data strongly suggest that the enrichment of LDL with cholesteryl esters and apo E, which occurs in hypercholesterolemic primates, is an atherogenic feature of the plasma lipoproteins.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The in vivo fate of β-very low density lipoproteins (β-VLDLs) was investigated after Cu2+-mediated oxidative modification (Ox-β-VLDL). Ox-β-VLDL may be physiologically relevant under conditions of defective VLDL removal by the liver (type HI hyperlipoproteinemia) or overloading of the remnant receptor (high cholesterol feeding). On oxidation of β-VLDL, the kinetics of its removal from the blood and uptake by the liver are unchanged. However, in contrast to β-VLDL, which is recognized by the remnant receptor of parenchymal cells, liver uptake of Ox-β-VLDL is mediated mainly by Kupffer cells (65% of liver-associated radioactivity). In vitro competition studies show that the cell association and degradation of iodine-125-labeled Ox-β-VLDL by both liver endothelial and Kupffer cells are only marginally competed for by acetylated LDL (10–20%), while an efficient blockade is noted with Ox-β-VLDL, oxidized low density lipoproteins, or polyinosinic acid (80–90%). The capacity of Kupffer cells to associate with and degradel2SI-Ox-β-VLDL appears to be twofold higher than for endothelial cells. It is concluded that on oxidation of β-VLDL, the recognition system responsible for the uptake of β-VLDL from the blood circulation is shifted from the remnant receptor to a specific oxidized-lipoprotein receptor. The efficiency of the scavenger activity on Kupffer cells will then form the protection system against the prolonged circulation of these atherogenic lipoproteins in the blood.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effects of high oleic acid rapeseed oil compared with polyunsaturated fats on serum lipoprotein levels are largely unknown. Therefore, we fed 30 women and 29 men a baseline diet rich in saturated fat, which was followed by a diet rich in high oleic and low erucic acid rapeseed oil (total energy content of fat, 38%; saturates, 12.4%; monounsaturates, 16%; n-6 polyunsaturates, 6%; and n-3 polyunsaturates, 2%) and one rich in sunflower oil (total energy content of fat, 38%; saturates, 12.7%; monounsaturates, 10%; n-6 polyunsaturates, 13%; and n-3 polyunsaturates, 0%). The oils were incorporated into mixed natural diets that were dispensed in a random order for 3.5 weeks each in a blinded crossover design. The diet composition was confirmed by analysis of duplicate diets. Both test diets reduced serum total cholesterol (TC) and low density lipoprotein (LDL) cholesterol levels from baseline, the monounsaturated rapeseed oil diet more than the polyunsaturated sunflower oil diet (TC: &#151;15% versus -12%,p<0.01; LDL cholesterol: -23% versus -17%,p<0.0l). Very low density lipoprotein (VLDL) cholesterol and total, VLDL, and LDL triglyceride levels were lower during the sunflower oil diet compared with the rapeseed oil diet Total high density lipoprotein (HDL) cholesterol levels remained unchanged by both diets. The consumption of rapeseed oil resulted in a more favorable HDLj to LDL cholesterol ratio (0.43±0.19 versus 0J9±0.18, /?<0.01) and an apolipoprotein A-I to B ratio (3.0±1.4 versus 2.4± 1.6,p<0.001) than did the sunflower oil. Our results suggest that substitution by high oleic acid rapeseed oil of saturated fats strongly affects LDL metabolism, whereas substitution by polyunsaturated sunflower oil affects both VLDL and in addition to LDL.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To examine the concentration of serum lipoproteins and the association of their genetic variation with the occurrence of coronary artery disease (CAD), composite serum lipoprotein profiles including lipoprotein(a) (Lp[a]), apolipoprotein (apo) E phenotypes, and apo BXba I genotypes were determined in patients with angiographically verified CAD (CAD+ group, n = 111) and in subjects with no angiographic evidence of CAD (CAD− group, n=46). In addition, we determined the concentrations of serum lipids, lipoproteins, and apolipoproteins in 96 healthy controls. Both CAD− and CAD+ groups had lower concentrations of apos A-I and A-II but higher concentrations of serum total and very low density lipoprotein triglyceride and very low density lipoprotein cholesterol than did healthy controls. The mean concentrations of serum total and low density lipoprotein cholesterol and the median values of Lp(a) were similar in the CAD+ and CAD− groups, both having higher concentrations of low density lipoprotein cholesterol and apo B than the healthy controls. Irrespective of gender, patients with CAD had significantly lower serum high density lipoprotein cholesterol than did those without CAD (1.48±0.40 versus 1.16±0.29 mmol/l,p<0.001). In women, the mean serum total and very low density lipoprotein triglyceride concentration was also higher in the CAD+ than in the CAD− group. The frequency of the apo E4 allele (&epsis;4) was significantly higher in the CAD+ group (0J93) than in the CAD− group (0.174;p<0.001). The frequencies of the two apo B alleles, XI (Xba I restriction site absent) and A X 2 (Xba I restriction site present), were similar in the two groups. Stepwise discriminant analysis revealed that in men, serum high density lipoprotein cholesterol had the highest power to discriminate for CAD. In addition, the concentration of plasma apo B levels and the occurrence of apo E phenotypes were independently associated with CAD in men. In women, the only independent factor associated with CAD after adjustment for β-blocker and diuretics usage was the concentration of serum triglycerides.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

B-mode ultrasound was used to noninvasively determine wall thickness and lumen diameter in the common carotid artery in patients with familial hypercholesterolemia (n=53) and in a control group (n=53). The controls were matched for sex, age, height, and weight, and all had a serum cholesterol level below 6.5 mmol/1. The study was performed to evaluate whether the patients had a thicker arterial wall compared with that of the control group. Wall thickness was determined as the combined intima-media thickness of the far wall and is presented as the mean and maximum thickness of a 10-mm-long section of the common carotid artery. The difference between the groups was 0.13 mm in mean wall thickness (p<0.001; 95% confidence interval, 0.07-0.18 mm) and 0.20 mm in maximum wall thickness (p<0.001; 95% confidence interval, 0.09-023 mm). Fifty of the subjects were examined twice to estimate the interobserver variability. The coefficients of variation for mean and maximum wall thickness were 102% and 8.9%, respectively. The two study groups were well matched and differed only in lipid levels. Thus, there is reason to believe that the difference in wall thickness can be explained by the background of familial hypercholesterolemia and the increased cholesterol levels.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

By Northern analysis, freshly isolated monocytes contained no detectable mRNA for monocyte chemotactic protein-1 (MCP-1). However, after 4 hours of incubation at 37°C, MCP-1 mRNA was clearly induced in the monocytes and was found to be highly dependent and directly proportional to the monocyte density. The level of MCP-1 mRNA continued to increase, reaching a peak after 22 hours of incubation. After 3 days in culture, MCP-1 mRNA levels had declined substantially and after 8 days were undetectable in the monocytes/macrophages. The amount of MCP-1 protein secreted correlated with the density-dependent increase in MCP-1 message. We hypothesize that the migration of monocytes into inflammatory lesions may be amplified by the density and time-dependent induction of MCP-1.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Proteoglycans were isolated from either grossly normal or atherosclerotic pigeon aortas after extraction with 4 M guanidlne hydrochloride and purification by ion-exchange and sizeexclusion chromatography. The small-size proteoglycans (Km, 0.4, on Sepharose CL-4B) from both normal and atherosclerotic tissue contained primarily a dermatan sulfate proteoglycan with an intact molecular size of 220-330 kd and a 45-kd core protein. In addition to the dermatan sulfate proteoglycan, the preparation contained a proteoglycan recognized by monoclonal antibody (MAb) 5-D-4, indicating the presence of sulfated poty-JV-acetyllactosamine sequences common to corneal and cartilage keratan sulfate. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gel revealed a polydisperse proteoglycan of 60-150 kd that was recognized by MAb 5-D-4. Significantly greater immunoreactivity with MAb 5-D-4 was observed for atherosclerotic compared with normal artery. After endo-β-D-galactosidase treatment of the proteoglycan from atherosclerotic aorta, diminished MAb 5-D-4 reactivity observed by both Western blot analysis and enzyme-linked immunosorbent assay demonstrated that the material was keratan sulfate. £ndo-β-D-galactosidase treatment of the intact proteoglycan generated core proteins of 28 and 38 kd. These studies suggest the presence of one or more keratan sulfate proteoglycans in grossly normal and atherosclerotic arteries. Immunochemical data suggest that sulfation of the keratan sulfate proteoglycan may be greater in atherosclerotic aorta.

ISSN:1049-8834    

出版商:OVID    

年代:1992

数据来源: OVID