bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits.
Authors: Rosenfeld M E , Tsukada T , Gown A M , Ross R
Published: June 2011

Morphologic and immunocytochemical studies were conducted to determine the sequence of cellular interactions that occur during the initiation of the fatty streak in the aorta of Watanabe Heritable Hyperlipemic rabbits and comparably hypercholesterolemic fat-fed rabbits. Watanabe rabbits from 3.5 weeks gestation to 2 months of age and fat-fed rabbits from 1 week to 2 months duration of hypercholesterolemia were compared utilizing light microscopic and scanning and transmission microscopic techniques. In both groups of animals, the earliest detectable events were an increase in monocyte adherence and subendothelial migration followed by formation of a single layer of intimal macrophage-derived foam cells. Immunocytochemical studies using macrophage-specific and muscle-actin-specific monoclonal antibodies support the morphologic data which suggests that the early fatty streak in both the Watanabe and fat-fed rabbits is predominantly composed of macrophage-derived foam cells. Thus, the absence of functional low density lipoprotein receptors in the Watanabe rabbit and differences in the distribution of cholesterol among the lipoproteins in the Watanabe and fat-fed rabbits do not appear to alter the initial responses of the cells of the artery wall to chronic hypercholesterolemia.
Hereditary hyperlipidemia and atherosclerosis in the rabbit due to overproduction of lipoproteins. II. Preliminary report of arterial pathology.
Authors: Seddon A M , Woolf N , La Ville A , Pittilo R M , Rowles P M , Turner P R , Lewis B
Published: June 2011

A genetically determined hyperlipidemic strain of New Zealand White rabbit that has features in common with combined familial hyperlipidemia in humans has been identified. The morphologic findings in a few animals fed a normal chow diet are reported. These consisted of macroscopically visible aortic intimal elevations found in the greatest number in the descending thoracic aorta. The plaques showed the presence of a cell population consisting of modified smooth muscle cells and lipid-laden macrophages. The lesion bases were necrotic and acellular, and some showed the presence of dystrophic calcification. Scanning electron microscopy revealed numerous monocytes attached to the endothelium. Endothelial defects were common, and these were filled with swollen and "ruffled" macrophages. Transmission electron microscopy confirmed the presence of lipid-laden cells penetrating between adjacent endothelial cells. These findings resemble those reported in a number of different animal species after dietary induction of hyperlipidemia. This strain is a useful new model for the study of atherogenesis.
Dipyridamole decreases platelet-derived growth factor levels in human serum.
Authors: Takehara K , Grotendorst G R , Silver R , LeRoy E C
Published: June 2011

Mitogenic activities on confluent fibroblasts by sera from patients with scleroderma and normal controls were studied. In experiments using eight different fibroblast strains (one human fetal lung fibroblast, one foreskin fibroblast, three adult skin fibroblast, and three scleroderma fibroblast), pooled scleroderma serum showed lower mitogenic activity by 3H-thymidine incorporation assay than pooled normal serum. Individual serum investigations revealed that 11 of 33 patients (33%) showed low mitogenic activities; all 11 patients were receiving dipyridamole. Of 15 patients, 11 (73%) receiving dipyridamole showed low mutagenic activities; none of 18 patients not receiving dipyridamole showed low mitogenic activities. Approximately 70% of this serum activity was inhibited by the addition of anti-platelet-derived growth factor (PDGF) antibody indicating that most of this serum activity seemed to be derived from PDGF. Western blot analysis of extracts of normal sera before and after administration of dipyridamole with antihuman PDGF antibody showed a large decrease in the amount of immunoreactive PDGF present. These data indicate that dipyridamole is an effective drug to lower release of PDGF during blood clotting.
Low density lipoprotein metabolism in human macrophages stimulated with microbial or microbial-related products.
Authors: Lopes-Virella M F , Klein R L , Stevenson H C
Published: June 2011

To determine whether stimulation of macrophages with products related to, or released as a consequence of, infectious processes could play a role in inducing the formation of foam cells, we studied the metabolism of native and acetylated low density lipoprotein (LDL) by human macrophages stimulated with lipopolysaccharide (LPS), muramyl dipeptide (MDP), polyinosinic:polycytidilic acid (Poly I:Poly C) and gamma-interferon. Cholesteryl ester (CE) synthesis by macrophages stimulated with LPS, MDP and Poly I:Poly C was markedly increased when the cells were incubated with native LDL (p less than 0.05). When incubated with acetylated LDL, LPS-stimulated macrophages showed a depression in CE synthesis (p less than 0.05). When incubated with acetyl-LDL, macrophages stimulated with Poly I:Poly C and gamma interferon showed a significant increase (p less than 0.05) in CE synthesis. The increase in CE synthesis by LPS-stimulated macrophages exposed to native LDL and by gamma-interferon-stimulated macrophages exposed to acetylated LDL was paralleled by an increase in cholesterol ester mass. The increase in CE synthesis and accumulation observed in LPS-stimulated macrophages incubated with native LDL seems to be due to an increase in the receptor mediated uptake of LDL. LPS inhibited and gamma-interferon activated the expression of the scavenger pathway in human macrophages. This may explain the changes observed in CE synthesis and accumulation when macrophages activated by the above stimuli were incubated with acetylated LDL. In conclusion, activation of human macrophages by some products released during, or as a consequence of, infectious processes led to an increase in CE synthesis and accumulation that may be relevant to the formation of "foam cells".
Accumulation of cholesteryl ester and lipid droplets in macrophages after uptake of cholesterol-rich necrotic products.
Authors: Wong H , Hashimoto S
Published: June 2011

The prevalence of degenerated cells in the thickened intima of cholesterol-fed animals suggested that necrotic regions might become a focus for lesion development by attracting histiocytes or monocytes. We propose that cholesterol-rich necrotic products scavenged by macrophages incite the accumulation of cholesteryl ester and the formation of cholesteryl ester droplets. The feasibility of this hypothesis was tested with readily available materials, namely, lung macrophages and plasma membrane vesicles (PMV) released from dying cholesterol-rich and normal hepatocytes. PMV from cholesterol-rich hepatocytes contained 30-fold more cholesteryl ester than PMV from normal hepatocytes. Degradation of 125I-PMV to trichloroacetic acid-soluble products by macrophages was fourfold higher than that of 125I-acetylated low density lipoprotein (acetyl-LDL) at 100 micrograms/ml of ligand in the incubation medium. Within this concentration range, degradation of PMV increased almost linearly with increasing concentrations of PMV, while the degradation of acetyl-LDL followed a saturation curve. Cholesterol-rich PMV increased the cholesteryl ester content of macrophages fourfold and augmented the incorporation of oleate threefold relative to normal PMV. These studies were extended to aortic smooth muscle cells. As with hepatocyte-PMV, smooth muscle cell-PMV was internalized and degraded by macrophages. The results suggested that cholesterol-rich necrotic materials could play a significant role in atherogenesis.
Modification of very low density lipoproteins leads to macrophage scavenger receptor uptake and cholesteryl ester deposition.
Authors: Mazzone T , Lopez C , Bergstraesser L
Published: June 2011

Chemically modified low density lipoproteins (LDL) are recognized by the macrophage scavenger receptor and can lead to substantial cholesteryl ester accumulation in cultured macrophages. Uptake of modified lipoproteins in vivo could contribute to foam cell formation during generation of the atherosclerotic plaque lesion. In the present study, modification of human pre-beta migrating very low density lipoprotein (VLDL) by acetylation led to recognition by the macrophage scavenger receptor as demonstrated in cross-competition experiments with acetylated LDL (ALDL). Recognition by this alternative binding site was associated with increased cholesterol delivery to human macrophages as assessed by suppression of LDL receptor activity, stimulation of cholesterol esterification rates, and accumulation of intracellular cholesteryl ester. Subfractionation of acetylated very low density lipoprotein (AVLDL) by ultracentrifugation in a discontinuous NaCl gradient demonstrated that AVLDL subfractions were equally effective in competing for 125I-ALDL uptake by macrophages when compared on the basis of particle number. These results suggest that modification of VLDL with subsequent recognition by the macrophage scavenger receptor may be a mechanism by which VLDL particles participate in macrophage cholesteryl ester overload.
Synthesis and secretion of plasma cholesteryl ester transfer protein by human hepatocarcinoma cell line, HepG2.
Authors: Faust R A , Albers J J
Published: June 2011

We have examined the synthesis, secretion, and functional and physical characteristics of a lipid transfer protein synthesized by a human hepatocellular carcinoma line. We found that this protein shares immunochemical determinants and many other properties with the lipid transfer protein, LTP-I, which has been purified from human plasma. We conclude that the human liver cell line, HepG2, synthesizes and secretes LTP-I. Thus, hepatocytes may be the source of LTP-I in human plasma.
Micropipette aspiration of cultured bovine aortic endothelial cells exposed to shear stress.
Authors: Sato M , Levesque M J , Nerem R M
Published: June 2011

The mechanical properties of cultured bovine aortic endothelial cells exposed to a fluid-imposed shear stress were studied using the micropipette technique. The cells, which were attached to a Thermanox plastic substrate, were exposed to a specific steady shear stress of either 10, 30, or 85 dynes/cm2 and for a duration ranging from 0.5 to 24 hours. Morphological changes in shape and orientation were observed, and following each experiment, the mechanical properties were measured using the micropipette aspiration technique applied to cells detached from the substrate. Fluorescent microscopy was carried out to observe cytoskeletal F-actin filaments stained with rhodamine phalloidin. During exposure to shear, the en face shape of the endothelial cells on the substrate became more elongated and their long axis became oriented to the direction of flow. There was also an alteration in the F-actin filaments. These changes were dependent on both the level of shear stress and the duration of exposure. After detachment, the cells exposed to shear maintained their deformed shape. This is in contrast to cells in a static, no-flow environment which became spherical in shape upon detachment. Cells exposed to shear stress demonstrated a mechanical stiffness significantly greater than that of control cells, which was dependent on both the level of shear stress and the duration of exposure. Furthermore, it appears that the influence of shear stress on endothelial cell mechanical stiffness may be related to alterations in cytoskeletal structure.
Distribution of von Willebrand factor in porcine intima varies with blood vessel type and location.
Authors: Rand J H , Badimon L , Gordon R E , Uson R R , Fuster V
Published: June 2011

The von Willebrand factor (vWF) has been generally accepted as a marker for endothelial cells. In a systematic immunolocalization study of porcine blood vessels that used indirect immunofluorescence with a monospecific polyclonal anti-vWF and two monoclonal anti-vWFs, we observed that vWF is not universally distributed in intact, fresh endothelia. vWF is consistently localized in veins, with the exception of the pulmonic vein. In arteries, vWF is generally absent except for areas of the distal abdominal aorta, the vaso vasorum of the thoracic aorta, and the pulmonic artery. We conclude that there are regional differences in the distribution of vWF in the various endothelial beds of pigs.
Deficiency of plasma protein S, protein C, or antithrombin III and arterial thrombosis.
Authors: Coller B S , Owen J , Jesty J , Horowitz D , Reitman M J , Spear J , Yeh T , Comp P C
Published: June 2011

Protein C and protein S are vitamin K-dependent coagulation factors that together act as an anticoagulant, and antithrombin III is a plasma protein that inhibits several activated factors in the coagulation cascade. Although deficiencies of any of these three proteins have been associated with deficiencies of these factors. We report one patient with a protein S deficiency, another with a protein C deficiency, and a third with an antithrombin III deficiency, each of whom who had extensive arterial thrombosis. We suggest that deficiencies of these proteins may constitute risk factors for arterial thrombosis.
Cigarette smoking and hypertension. Factors independently associated with blood hyperviscosity and arterial rigidity.
Authors: Levenson J , Simon A C , Cambien F A , Beretti C
Published: June 2011

The effects of cigarette smoking and hypertension on hemorheological variables (blood viscosity over a wide range of shear rates, plasma viscosity, microhematocrit, and plasma protein concentration) and on arterial stiffness (pulse wave velocity) were investigated in 33 normotensive men and 81 mild to moderately hypertensive men. Of these, 22 normotensive and 24 hypertensive subjects were cigarette smokers. Cigarette smoking and hypertension were independently associated with higher blood viscosity at all studied shear rates (from 0.2 to 241 sec-1) as well as with higher plasma viscosity, hematocrit, and pulse wave velocity. At constant hematocrit levels, hypertension remained associated with a higher blood viscosity, while the association with cigarette smoking disappeared. Normotensive smokers had the same increase of blood and plasma viscosity and pulse wave velocity as hypertensive nonsmokers. No interactive effects of hypertension or cigarette smoking on blood or arterial variables were observed, suggesting that the effect of these two factors on blood and vascular rheology are cumulative. Smoking and hypertension may change the flow properties of the blood and the behavior of the arterial wall and this may explain the arterial damage observed in cigarette smokers and hypertensive patients.
Effect of verapamil on cholesteryl ester hydrolysis and reesterification in macrophages.
Authors: Stein O , Stein Y
Published: June 2011

The macrophage-like cell line, J774, and its variant, CT2, were used to study the effect of verapamil on metabolism of esterified cholesterol. The cells had been labelled with 3H-cholesterol for 24 hours and thereafter acetylated low density lipoprotein (LDL) or d less than 1.019 g/ml fraction of hypercholesterolemic rabbit plasma was added. After an additional 24 hours, 60% or 40% of the label, respectively, was recovered in esterified cholesterol in control dishes, but only 2% to 15%, in the presence of 50 microM verapamil. Enhancement of esterification of cellular 3H-cholesterol was also obtained by addition of liposomes with a cholesterol/phosphatidylcholine molar ratio of 2:1. This reaction was almost completely inhibited by compound 58-035, an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, while addition of verapamil resulted in a dose-dependent partial inhibition which was evident after 4 hours. To determine whether the reduction in cholesterol esterification was due to a direct inhibition of ACAT or to an effect of verapamil on the transport of cholesterol to the site of ACAT activity, the cells were incubated with acetylated LDL labelled with 3H-cholesteryl ester, and the amount of uptake, lysosomal hydrolysis, and cytoplasmic reesterification was determined. In control cells and in cells exposed to the ACAT inhibitor, more than 98% of the 3H-cholesteryl ester taken up had been hydrolyzed. Reesterification of 3H-cholesterol was negligible in the presence of the ACAT inhibitor and amounted to 37.1% in control cells. When verapamil was present, reesterification of 3H-cholesterol to cholesteryl ester was only 4%, while the amount of 3H-cholesteryl ester hydrolyzed was 58% of that taken up.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidemiology of aortic aneurysms: I. Mortality trends in the United States, 1951 to 1981.
Authors: Lilienfeld D E , Gunderson P D , Sprafka J M , Vargas C
Published: June 2011

The trends in mortality from aortic aneurysms in the United States from 1951 through 1981 were studied. Annual age-specific and age-adjusted mortality for aortic aneurysms were calculated for white males, white females, nonwhite males, and nonwhite females. For all four groups, a constant increase in age-adjusted mortality was noted for the period 1951 to 1968 (an average annual increase of 17% for white males, 12% for white females, 14% for nonwhite males, and 15% for nonwhite females), plateauing in 1968, with a slight decline noted after 1968. The increase corresponded to an increase in the total number of U.S. aortic aneurysm deaths from about 2500 to approximately 14,000. The decline was most notable for dissecting aneurysms. Analysis of the age-specific rates by birth cohort suggests that mortality is increasing with each subsequent cohort. Analysis of specific aneurysm types (dissecting, thoracic, abdominal, and not otherwise specified) suggests that abdominal ones are most common. These data are reviewed in the context of existing knowledge of aortic aneurysms. Further studies to validate these findings and to develop hypotheses for the etiology of aortic aneurysms are needed.
Deferred effects of preweaning diet on atherosclerosis in adolescent baboons.
Authors: Lewis D S , Mott G E , McMahan C A , Masoro E J , Carey K D , McGill H C
Published: June 2011

We examined the effects of breast and formula feeding during infancy on the serum lipoproteins and on atherosclerosis in young adult baboons. Baboons were breast-fed (n = 13) or formula-fed (n = 32) until weaning at 16 weeks of age and thereafter they were fed a diet containing 1.7 mg cholesterol/kcal and 40% of calories as lard until 5 years of age. At 12 weeks of age, breast-fed baboons had higher serum high density lipoprotein cholesterol concentration (HDL-C, 68 vs. 51 mg/dl), lower serum triglyceride concentration (37 vs. 68 mg/dl), and lower very low density plus low density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C ratio (0.65 vs. 0.98) than formula-fed infants. From weaning to 92 weeks of age, breast-fed baboons had a lower serum triglyceride concentration (23 vs. 38 mg/dl) than formula-fed baboons. After weaning, the VLDL + LDL-C/HDL-C ratio increased from 0.65 to 1.0 in breast-fed baboons, but decreased from 0.98 to 0.72 in formula-fed baboons. From 92 to 246 weeks of age, the VLDL + LDL-C/HDL-C ratio was consistently higher in breast-fed baboons compared to formula-fed baboons. At 5 years of age, baboons breast-fed as infants had a greater percentage of intimal surface area involved with atherosclerosis in the abdominal aorta, the iliac-femoral artery, the aortic arch, the brachial artery, and the carotid artery, than did those formula-fed as infants. The greater prevalence of lesions in breast-fed baboons was explained mainly by the higher VLDL + LDL-C/HDL-C ratio.
Effects of flow pulsatility on platelet adhesion to subendothelium.
Authors: van Breugel H H , Sixma J J , Heethaar R M
Published: June 2011

Platelet adhesion in the annular perfusion system developed by Baumgartner was studied under pulsatile, oscillatory, or steady flow conditions. To investigate in what way pulsatile flow affects platelet adhesion, we developed a flow system that produces a sinusoidal laminar flow superimposed on a constant component in the annular perfusion chamber. Frequencies and amplitudes of this sinusoidal flow were in the physiological range. Pulse frequencies varied between 30 and 120 beats/minute, and different amplitudes of the wall shear rate in the range 75 to 1000 s-1 were studied. Shear rates resulting from the constant flow component were between 500 s-1 and 1800 s-1. Under these conditions, no significant differences in platelet adhesion were observed between steady flow and pulsatile flow. In the case of an oscillatory flow (absence of constant component), a clear dependence of platelet adhesion on the amplitude of the pulse was seen. These data indicate that platelet adhesion in larger blood vessels, such as the aorta and larger arteries where backflow is limited, is not essentially influenced by the pulsatility in these vessels.
Heredity and changes in plasma lipids and lipoproteins after short-term exercise training in men.
Authors: Després J P , Moorjani S , Tremblay A , Poehlman E T , Lupien P J , Nadeau A , Bouchard C
Published: June 2011

The aims of this controlled experiment were to investigate the effects of short-term aerobic exercise training on plasma lipid and lipoprotein concentrations and the role of heredity in determining the individual variation observed in the lipoprotein-lipid response. Six pairs of male monozygotic (MZ) twins were subjected to an exercise training program that induced a 22,000 kcal energy deficit after 22 consecutive days of training. This program significantly reduced body weight, percent body fat, and subcutaneous fat and significantly increased maximal oxygen consumption (VO2max) (p less than 0.005). The plasma insulin response to an oral glucose challenge was markedly reduced after training (p less than 0.001). Plasma triglyceride concentration decreased and the high density lipoprotein cholesterol (HDL-CHOL)/CHOL ratio increased with training (p less than 0.05). Subjects also displayed substantial individual variation in their response to exercise training, but the changes in plasma CHOL, apolipoprotein (apo) B low density lipoprotein cholesterol (LDL-CHOL), HDL-CHOL, and the HDL-CHOL/CHOL ratio tended to be similar within MZ twin pairs (0.67 less than or equal to ri less than or equal to 0.92; 0.05 greater than p less than 0.0001) thus indicating a significant effect of heredity on the sensitivity of plasma lipids and lipoproteins to exercise training.(ABSTRACT TRUNCATED AT 250 WORDS)
Reduced atherogenesis in cholesterol-fed diabetic rabbits. Giant lipoproteins do not enter the arterial wall.
Authors: Nordestgaard B G , Stender S , Kjeldsen K
Published: June 2011

In cholesterol-fed rabbits, alloxan-diabetes has an anti-atherogenic effect, which is associated with severe elevation of plasma triglyceride concentrations. To study this effect, we measured lipoprotein sizes and aortic permeability coefficients for cholesteryl ester and for albumin in hypertriglyceridemic diabetic cholesterol-fed rabbits and in normotriglyceridemic cholesterol-fed rabbits. With the same high cholesterol concentration in plasma, hypertriglyceridemic diabetic rabbits had 70% of plasma cholesterol in very large lipoproteins (diameter greater than 75 nm), whereas normotriglyceridemic rabbits had only about 10% of plasma cholesterol in these giant lipoproteins. The aortic permeability coefficients for cholesteryl ester in hypertriglyceridemic diabetic cholesterol-fed rabbits was only 10% to 50% of that in normotriglyceridemic cholesterol-fed rabbits. Aortic permeability coefficients for albumin did not differ significantly between the hypertriglyceridemic and normotriglyceridemic rabbits. The results suggest that the large size of a major fraction of plasma lipoproteins in the hypertriglyceridemic diabetic cholesterol-fed rabbits is responsible for the relatively low aortic permeability coefficient for cholesteryl ester from plasma and hence for reduced atherogenesis in these animals.
Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis.
Authors: Huff M W , Breckenridge W C , Strong W L , Wolfe B M
Published: June 2011

The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline.(ABSTRACT TRUNCATED AT 250 WORDS)
Biosynthesis of chondroitin sulfate proteoglycan by P388D1 macrophage-like cell line.
Authors: Christner J E
Published: June 2011

Macrophages are in large part responsible for the subendothelial deposition of lipid within the artery wall during the early stages of atherogenesis. Proteoglycans secreted by these cells may play a role in this pathological process either by trapping lipoproteins in the extracellular matrix or by enhancing the formation of lipid-laden foam cells. The synthesis and secretion of proteoglycan was studied in the P388D1 macrophage-like cell line cultured in the presence of 35S-sulfate. The radiolabeled proteoglycan had a Kd of 0.69 on Sepharose CL-2B corresponding to an Mr of 2.8 x 10(5). It consisted of approximately 13 chondroitin sulfate chains of Mr 20,000 attached to a core protein with an Mr of 18,000. The chondroitin sulfate chains contained both N-acetylgalactosamine 6-sulfate and N-acetylgalactosamine 4-sulfate residues. No disulfated N-acetylgalactosamine residues were present. The P388D1 proteoglycan bound specifically to immobilized human low density lipoprotein. These results suggest that, in the focal regions of the arterial wall in which macrophages are found during the development of fatty streaks, proteoglycans secreted by these cells may affect the transport and cellular metabolism of plasma-derived lipids.
Prevalence of carotid atherosclerosis and serum cholesterol levels in eastern Finland.
Authors: Salonen R , Seppänen K , Rauramaa R , Salonen J T
Published: June 2011

We investigated the prevalence of carotid atherosclerosis and its association with serum lipoprotein cholesterol fractions in 412 Eastern Finnish men ages 42, 48, 54, or 60 years who were examined between February and December 1987 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Carotid atherosclerosis was assessed with high-resolution B-mode ultrasonography. Of the participants, 37% had thickening of the intimal or medial layer of the arterial wall, 10% had plaques, 2% had stenosis in the right or left common carotid artery or in the carotid bifurcation, and only 51% were free of any detectable carotid atherosclerosis. The prevalence of atherosclerosis was 14.1%, 32.0%, 67.7%, and 81.9% in the four age groups, respectively. The mean age-adjusted serum low density lipoprotein (LDL) cholesterol concentration was 3.67 mmol/l (142 mg/dl) in men free of carotid atherosclerosis and 4.02 mmol/l (155 mg/dl) in those with at least intimal thickening (p = 0.003 for difference). The mean age-adjusted serum cholesterol concentration in the high density lipoprotein (HDL) fraction was 1.34 mmol/l (52 mg/dl) in the atherosclerosis-free and 1.27 mmol/l (49 mg/dl) in the atherosclerotic men (p = 0.029 for difference). There was a similar difference in both the serum HDL2 and the HDL3 cholesterol levels. Serum LDL and HDL (inverse) cholesterol were significant determinants of severity of carotid atherosclerosis in a multivariate regression model adjusting for age, obesity, plasma fibrinogen, cigarette-years, and duration of hypertension. Our data reveal the high prevalence of atherosclerosis in middle-aged Eastern Finnish men and provide further evidence of the roles of LDL and HDL cholesterol in atherosclerosis.
Assessment of cardiovascular risk factors in Nigerian students.
Authors: Adams-Campbell L L , Nwankwo M U , Omene J A , Ukoli F A , Young M P , Haile G T , Kuller L H
Published: June 2011

The present study assessed the prevalence of cardiovascular risk factors in 65 Nigerian medical students attending the University of Benin, Benin City, Nigeria. Their ages ranged from 17 to 28 years with a mean age for men of 20.9 years and for women of 18.8 years. Approximately 8% of the men and 0% of the women were current cigarette smokers, whereas alcohol use was observed in 14.6% of the men and in 0% of the women. The Nigerian men had significantly higher diastolic blood pressures than did American black and white men. Compared to American black men, the Nigerian men had considerably lower total cholesterol and triglyceride concentrations. The Nigerian women did not differ from American black women with respect to total cholesterol, but had significantly lower triglyceride concentrations.
Cell biology of arterial proteoglycans.
Authors: Wight T N
Published: June 2011

Although proteoglycans constitute a minor component of vascular tissue, these molecules have been shown to influence a number of arterial properties such as viscoelasticity, permeability, lipid metabolism, hemostasis, and thrombosis. A hallmark of early and late atherosclerosis is the accumulation of proteoglycans in the intimal lesions. Yet, it is not clear why this accumulation occurs. This article reviews the classes of proteoglycans synthesized by the two major cell types of the arterial wall--the endothelial and smooth muscle cell. Detailed consideration is then given to the modulation of proteoglycan metabolism and the role that proteoglycans play in a number of cellular events such as adhesion, migration, and proliferation--important processes in both the development and the pathogenesis of blood vessels. Last, the involvement of proteoglycans in two critical vascular wall processes--hemostasis and lipid metabolism--is reviewed, because these events pertain to atherogenesis. This review emphasizes the importance of proteoglycans in regulating several key events in normal and pathophysiological processes in the vascular tissue.
Association of decreased sex hormone binding globulin and cardiovascular risk factors.
Authors: Haffner S M , Katz M S , Stern M P , Dunn J F
Published: June 2011

Sex hormones play a major role in determining the risk of cardiovascular disease. While earlier studies have shown that reduced sex hormone binding globulin (SHBG) is associated with increased glucose and insulin concentrations in premenopausal women, few data exist on the relationship of SHBG to other cardiovascular risk factors in women. We hypothesized that decreased SHBG would be associated with an atherogenic pattern of cardiovascular risk factors. We measured total testosterone, total estradiol and SHBG, lipids and lipoproteins, glucose and insulin, and systolic and diastolic blood pressure in 96 premenopausal women. Although total testosterone and total estradiol were not related to cardiovascular risk factors, SHBG was negatively associated with triglyceride concentration (r = -0.37) and positively associated with high density lipoprotein cholesterol (HDLC) (r = 0.42). After adjustment for overall adiposity (body mass index) and upper body adiposity (as measured by the ratio of waist-to-hip circumferences), SHBG was still positively related to HDLC, but not to triglyceride. Adjustment for insulin abolished the relationship between SHBG and triglyceride levels, but did not alter the relationship between SHBG and HDLC. Sex hormones were not related to either systolic or diastolic blood pressure.
Effect of fibrin on endothelial cell production of prostacyclin and tissue plasminogen activator.
Authors: Kaplan K L , Mather T , DeMarco L , Solomon S
Published: June 2011

Fibrin formed on endothelial cells has previously been shown to have deleterious effects on the cells. Additionally, substances that cause endothelial cell damage have been reported to induce cultured endothelial cells to synthesize prostacyclin and tissue plasminogen activator (t-PA). The present studies were undertaken to determine whether fibrin formed on cultured human umbilical vein endothelial cells would alter synthesis of prostacyclin and t-PA by the cells. Fibrin was found to increase synthesis of both prostacyclin and t-PA in a dose and time dependent manner. Stimulation of prostacyclin synthesis was completely inhibited by indomethacin; partially inhibited by actinomycin D, cycloheximide, and trifluoperazine; and not affected by cytochalasin D or vinblastine. In contrast, stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide; partially inhibited by cytochalasin D, vinblastine, and trifluoperazine; and not affected by indomethacin. Fibrin I, formed with Reptilase, caused only slight stimulation of t-PA production, but virtually no stimulation of prostacyclin synthesis. Neither collagen polymerization on the cells nor thrombin added in concentrations that did not induce fibrin polymer formation stimulated production of either substance. Furthermore, soluble fibrin II generated in the presence of the fibrin polymerization inhibitor gly-pro-arg-pro also failed to stimulate either prostacyclin or t-PA production. The presence of platelets in the plasma from which the fibrin was formed did not affect the amount of stimulation of the cells. Fibrin-induced stimulation of endothelial cell production of prostacyclin and t-PA could act to limit vascular occlusion in vivo by inhibiting platelet function and by stimulating fibrinolysis via t-PA.
Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages.
Authors: Aviram M , Williams K J , McIntosh R A , Carpentier Y A , Tall A R , Deckelbaum R J
Published: June 2011

Intralipid is widely used for intravenous alimentation and contains triglyceride-emulsion particles and phospholipid liposomes. After infusion, triglyceride-emulsion particles resemble chylomicron remnants and thus may be atherogenic. On the other hand, intravenous infusion of phospholipid liposomes produces regression of experimental atherosclerosis and abolishes the ability of hypercholesterolemic rabbit plasma to cholesterol-load cultured macrophage foam cells. To determine the net effect of intralipid infusion on cellular cholesterol balance, J-774 macrophages were incubated for 18 hours with human serum obtained before, during, and after a 6-hour infusion of 10% Intralipid. Compared to serum-free medium, pre-infusion serum increased cellular unesterified cholesterol by 76% and cholesteryl ester by 78%. In contrast, serum obtained after the 6-hour infusion reduced cellular unesterified cholesterol by 23% and cholesteryl ester by 15%. Serum obtained 18 hours after the end of the infusion still showed impaired cholesterol-loading ability. Mouse peritoneal macrophages incubated with these serum samples behaved similarly. Compared to pre-infusion serum, postinfusion serum inhibited cellular uptake of 125I-low density lipoprotein and 125I-very low density lipoprotein by 50% and 80%, respectively, and also enhanced the efflux of cellular cholesterol by 46%. We conclude that the ability of human serum to cause cholesterol accumulation in cultured macrophages is abolished by an infusion of Intralipid. This effect is mediated by a reduction in cholesterol uptake by the cells and by an increase in cell cholesterol efflux. If similar events occur in the arterial wall, Intralipid infusion might inhibit foam cell formation in vivo.
Structure of apolipoprotein B-100 of human low density lipoproteins.
Authors: Yang C Y , Gu Z W , Weng S A , Kim T W , Chen S H , Pownall H J , Sharp P M , Liu S W , Li W H , Gotto A M
Published: June 2011

We have analyzed low density lipoproteins (LDL) apolipoprotein (apop) B structure by direct sequence analysis of LDL apo B-100 tryptic peptides. Native LDL were digested with trypsin, and the products were fractionated on a Sephadex G-50 column. The partially digested apo B-100 still associated with lipids was recovered in the void volume (designated trypsin-nonreleasable, TN, peptides). The released peptides (designated trypsin-releasable, TR, peptides) in subsequent peaks were repurified on two successive high-performance liquid chromatography (HPLC) columns. The TN peak was delipidated and redigested with trypsin, and the resulting peptides were purified on two successive HPLC columns. Using this approach, we sequenced over 88% of LDL apo B-100, extending and refining our previous study (Nature 1986;323:738-742) which covered 52% of the protein. TN peptides made up 31%, and the TR peptides, 34% of the apo B-100 sequence; 23.7% were found under both TN and TR categories. Based on its differential trypsin releasability, apo B-100 can be divided into five domains: 1) residues 1----1000, largely TR; 2) residues 1001----1700, alternating TR and TN; 3) residues 1701----3070, largely TN; 4) residues 3071----4100, mainly TR and mixed; and 5) residues 4101----4536, almost exclusively TN. Domain 1 contained 14 of the 25 Cys residues in apo B. Domain 4 encompassed seven N-glycosylation sites, and contained the putative receptor binding domains. All 19 potential N-glycosylation sites were directly sequenced: 16 were found to be glycosylated and three were not. Three pairs of disulfide bridges were also mapped. Finally, a combination of cDNA sequencing, direct mRNA sequencing, and comparison of published apo B-100 sequences allowed us to identify specific amino acid residues within apo B-100 that seem to represent bona fide allelic variations. Our study provides information on LDL apo B-100 structure that will be important to our understanding of its conformation and metabolism.
Functional behavior of vessels from pigs with von Willebrand disease. Values of platelet deposition are identical to those obtained on normal vessels.
Authors: Badimon L , Badimon J J , Turitto V T , Rand J , Fuster V
Published: June 2011

Vessels from normal pigs and pigs with severe von Willebrand disease were exposed for up to 30 minutes to both nonanticoagulated and heparinized blood from normal pigs in an ex vivo perfusion system. Shear rates at the vessel surface were varied over a broad physiological range, gamma w = 212 to 3380 sec-1. The deposition of 111In-labeled platelets was determined by radiometric counting. For all shear rates and exposure times investigated, the levels of platelet deposition on de-endothelialized thoracic aorta of normal and von Willebrand disease pigs were not significantly different. Thus, the functional activity of the vessels correlated with the results obtained previously by immunofluorescence. Namely, the von Willebrand factor protein in the thoracic subendothelium of normal pigs is significantly diminished or absent and is comparable to the levels observed in von Willebrand disease pigs.
Development of atherosclerosis in genetically hyperlipidemic rabbits during chronic fish-oil ingestion.
Authors: Rich S , Miller J F , Charous S , Davis H R , Shanks P , Glagov S , Lands W E
Published: June 2011

The evidence for a reduction in cardiovascular mortality from fish oil is based on epidemiologic observations. To test whether fish-oil supplementation influences the development of atherosclerosis, we treated Watanabe heritable hyperlipidemic rabbits (WHHL), an inbred strain that spontaneously develops atherosclerosis, with 2.5 ml of MaxEPA fish-oil concentrate daily and compared them to a control group fed unsupplemented rabbit chow. Serial cholesterol and triglyceride levels were monitored as were plasma lipid hydroperoxides. The animals were given fish oil from the time of weaning until 1 year of age, when they were sacrificed and their aortas were compared for the extent of atherosclerosis. No significant differences in the cholesterol or triglyceride levels were noted between the two groups. Fatty acid hydroperoxide levels were also similar and were noted to increase from weaning (1.0 +/- 0.7 microM) to the time of sacrifice (1.8 +/- 1.5 microM, p less than 0.01). Fish oil had no influence on the extent of aortic atherosclerosis (25% +/- 14% surface area for controls vs. 28% +/- 19% for treated, p = NS), plaque thickness, or plaque volume after 1 year. We conclude that fish oil does not reduce the levels of serum cholesterol, lipid hydroperoxides, or aortic atherosclerosis in WHHL rabbits. The hypothesis that fish oil protects against atherosclerosis was not supported by this study.
Adipose tissue distribution and plasma lipoprotein levels in obese women. Importance of intra-abdominal fat.
Authors: Després J P , Moorjani S , Ferland M , Tremblay A , Lupien P J , Nadeau A , Pinault S , Thériault G , Bouchard C
Published: June 2011

Prospective studies have shown that excess abdominal fat is associated with an increased risk of coronary heart disease and related death. We used computed axial tomography (CAT) to assess the association between deep and subcutaneous abdominal adipose tissue and plasma lipoprotein levels in a sample of 52 premenopausal obese women aged 35.7 +/- 5.5 years (mean +/- SD). Whereas the plasma lipoprotein concentration were not significantly correlated with fat mass, the data obtained by CAT indicated that the absolute amount of deep abdominal fat was negatively correlated with high density lipoprotein cholesterol (HDL-CHOL) levels (r = -0.35, p less than 0.01), as well as with HDL-CHOL/low density lipoprotein (LDL)-CHOL, HDL-apoprotein-(apo) A-I/LDL-apo B, and HDL2-CHOL/HDL3-CHOL ratios (-0.32 less than or equal to r less than or equal to -0.40, 0.05 greater than p less than 0.01). Adipose tissue deposition at the mid-thigh region determined by CAT did not show any significant relationship with plasma lipoprotein levels. When subgroups of women with comparable ages and adiposity but with high and low intra-abdominal fat accumulation were compared, women with a high accumulation of intra-abdominal fat displayed significantly lower HDL-CHOL (p less than 0.001), HDL2-CHOL (p less than 0.001), HDL3-CHOL (p less than 0.01), and HDL-apo A-I (p less than 0.05) levels, as well as reduced HDL-CHOL/LDL-CHOL (p less than 0.01), HDL-apo A-I/LDL-apo B (p less than 0.05), and HDL2-CHOL/HDL3-CHOL ratios (p less than 0.05) in comparison with obese women with low accumulations of intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)
A possible mechanism for accelerated atherogenesis in male versus female rats.
Authors: Staprans I , Felts J M
Published: June 2011

Dietary fat and cholesterol enter the circulation as chylomicrons. They are removed from the circulation by attachment to lipoprotein lipase located on the endothelial surfaces. As the result of lipoprotein lipase action, chylomicrons are partially hydrolyzed and then reenter the circulation as remnants, which are rapidly cleared by the liver. We investigated the fate of 3H-retinol- and 14C-cholesterol-labeled chylomicrons injected into male and female rats. The disappearance curves of chylomicrons from the circulation were not significantly different in males and females, which suggests that translocation from plasma to endothelium is similar for both sexes. However, in male rats, the "dwell time" of chylomicrons on the endothelium was significantly prolonged. At 10 and 20 minutes after chylomicron injection, more label was found in the livers of female than male rats. The opposite was true for hearts. Male hearts contained significantly more endothelium-bound chylomicrons when compared with female hearts. This increase in dwell time may allow greater cholesterol deposition in the endothelium of male rats. The more rapid processing of chylomicrons was associated with a 300% greater postheparin lipoprotein lipase in female rats, which suggests a greater enzyme density at chylomicron attachment points on endothelium.
Balloon catheter injury to rabbit carotid artery. II. Selective increase in reactivity to some vasoconstrictor drugs.
Authors: Manderson J A , Cocks T M , Campbell G R
Published: June 2011

The present study examined the changes in reactivity to a variety of vasoconstrictor drugs of the rabbit carotid artery during development of an intimal thickening induced by injury with an inflated balloon catheter. The injured and the unoperated contralateral carotid arteries were studied at 2 and 6 weeks after the operation. To differentiate areas of the injured artery lined by modified smooth muscle cells from areas lined by regenerated endothelial cells, each rabbit was injected with Evans blue dye before sacrifice. Ring segments (3 mm length) from the control and injured arteries were mounted in organ baths to record the circumferential isometric force with a technique that ensured that all rings were set to equivalent initial resting conditions of passive transmural stretch. Compared with the controls, the experimental arteries had a significantly decreased maximum contraction (Emax) in response to KCl at both 2 and 6 weeks. The experimental arteries were also significantly less sensitive to the alpha 1-adrenoceptor agonist, methoxamine, at both 2 weeks (approximately sevenfold) and 6 weeks (fourfold), with a marked decrease in Emax at 2 weeks, which returned to control values at 6 weeks. There was no change in Emax to either serotonin or the thromboxane A2-mimetic, U46619, in the experimental arteries at either time. There was, however, a small but significant increase in the sensitivity to both drugs. There was no difference in response to any of the constrictor agents between the white and blue regions of the experimental vessels.(ABSTRACT TRUNCATED AT 250 WORDS)