bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiologic and supraphysiologic increases in lipoprotein lipids and apoproteins in late pregnancy and postpartum. Possible markers for the diagnosis of "prelipemia".
Authors: Montes A , Walden C E , Knopp R H , Cheung M , Chapman M B , Albers J J
Published: June 2011

A supraphysiologic (greater than 95th percentile) rise in plasma lipids in pregnancy may serve as a marker for "prelipemia" in the same way that gestational diabetes is a marker for prediabetes. To qualify as prelipemic, subjects with an abnormal lipid rise antepartum must return to normal postpartum but may have other identifying characteristics. This paper describes the antepartum-postpartum changes of lipoprotein lipids and apoproteins at 34 to 38 weeks of gestation and 6 and 20 weeks postpartum in 23 subjects with physiologic and six subjects with supraphysiologic plasma lipid increases during pregnancy. These results are compared to measurements in 23 nonpregnant controls matched for weight, age, and race. In subjects with a physiologic antepartum lipid rise, postpartum total triglyceride and very low density lipoprotein (VLDL) lipids (cholesterol and triglyceride) and apo B returned to baseline within 6 weeks. In contrast, low density lipoprotein (LDL) showed a slow postpartum decline in lipids and apo B with elevations remaining at 20 weeks postpartum. High density lipoprotein (HDL) cholesterol concentrations, elevated in pregnancy, remained elevated at 6 weeks postpartum, but fell to baseline by 20 weeks postpartum. HDL triglyceride and apo A-l concentrations, both elevated in pregnancy, returned to baseline by 6 weeks postpartum. A supraphysiologic triglyceride rise in pregnancy was associated with a slower return of total triglycerides and VLDL to baseline, reduced HDL cholesterol ante- and postpartum, atypical changes in LDL cholesterol during pregnancy and postpartum, and evidence of hyperlipidemia among family members. Two subjects with hypercholesterolemia in the nonpregnant state showed no marked exaggeration of total or LDL cholesterol concentrations in pregnancy. The data support the hypothesis that a supraphysiologic rise in plasma triglyceride concentrations in late pregnancy may serve as a marker of prelipemia. Proof of the hypothesis requires further investigation and longer follow-up.
New approaches to thrombolytic therapy.
Authors: Collen D , Lijnen H R
Published: June 2011

Tissue-type plasminogen activator (t-PA), purified from the culture fluid of a stable human melanoma cell line, is a serine protease, different from urokinase, with a molecular weight of about 70,000. It is composed of one polypeptide chain, which is converted to a two-chain molecule by limited plasmic action. Activation of plasminogen to plasmin occurs by cleavage of the Arg 560-Val 561 peptide bond. Kinetic analysis has shown that the activation obeys Michaelis-Menten kinetics and that the presence of fibrin strikingly enhances the activation rate by increasing the affinity of plasminogen for fibrin-bound t-PA. The directed action of plasmin toward fibrin in vivo, might be explained by the low Michaelis constant in the presence of fibrin (0.16 microM), which allows efficient plasminogen activation on a fibrin clot, while its high value in the absence of fibrin (65 microM) prevents efficient activation in plasma. Plasmin formed on the fibrin surface would then be protected from rapid inactivation by alpha 2-antiplasmin. An important consequence of this molecular model for physiological fibrinolysis is that specific thrombolysis is only expected with the use of a specific plasminogen activator, which confines activation to the fibrin surface. Studies on the thrombolytic properties of purified t-PA in various animal species and in humans have revealed a higher specific thrombolytic activity than urokinase. Thrombolysis could be achieved without causing significant plasminogen activation, alpha 2-antiplasmin consumption, or fibrinogen breakdown. Alternatively, pro-urokinase, the zymogen precursor of urokinase, also displays a certain degree of fibrin specificity. Its mechanism of action and potential therapeutic value remain to be established.
Impaired glucose tolerance and risk factors for atherosclerosis.
Authors: Vaccaro O , Rivellese A , Riccardi G , Capaldo B , Tutino L , Annuzzi G , Mancini M
Published: June 2011

This study attempts to evaluate whether the putative excess risk of cardiovascular disease in individuals with impaired glucose tolerance (IGT) can be explained by the clustering of other major cardiovascular risk factors after controlling for obesity. The study population was 1376 male and female employees of a Naples telephone company who had participated in a health survey in which an oral glucose tolerance test (OGTT) was given. After excluding treated hypertensives, we recruited all 65 individuals with IGT and 125 euglycemic controls matched for gender, age, and weight. Systolic and diastolic blood pressure was significantly higher in individuals with IGT (134 +/- 16 vs 127 +/- 15 mm Hg, p less than 0.001; 87 +/- 10 vs 84 +/- 8 mm Hg, p less than 0.05 (M +/- SD). Blood lipids were similar in the two groups (total cholesterol was 214 +/- 34 vs 218 +/- 40 mg/dl; HDL cholesterol was 39 +/- 9 vs 40 +/- 10 mg/dl; total triglyceride was 145 +/- 58 vs 135 +/- 63 mg/dl). Serum insulin values (fasting or at 1 or 2 hours after 75 g of oral glucose) were also similar. The number of persons currently smoking was significantly lower among individuals with IGT (30% vs 47%, p less than 0.025) but the percentage of exsmokers was identical in the two groups. We conclude that, among the possible cardiovascular risk factors investigated, blood pressure is the only one significantly associated with IGT independent of matched variables and antihypertensive treatment.
Low density lipoprotein metabolism in familial combined hyperlipidemia. Mechanism of the multiple lipoprotein phenotypic expression.
Authors: Kissebah A H , Alfarsi S , Evans D J
Published: June 2011

Plasma low density lipoprotein (LDL) kinetics and their relation to plasma very low density lipoprotein (VLDL) and LDL composition were determined in patients with familial combined hyperlipidemia (FCHL) of varying lipoprotein phenotypes. In both Type II and IV subjects, LDL apolipoprotein B (apo B) synthesis was greater than normal. In Type IV, the VLDL triglyceride/apo B ratio was normal and almost all of the LDL apo B was derived from VLDL. LDL cholesterol/apo B ratio was diminished and LDL apo B fractional catabolic rate (FCR) was sufficiently increased to prevent a rise in plasma LDL concentration. In Type II, VLDL triglyceride/apo B was reduced and 14% to 50% of the LDL was formed by direct synthesis. LDL cholesterol/apo B was normal and LDL apo B FCR was lower than in Type IV subjects. In four patients whose plasma lipid levels became normal with carbohydrate restriction and intake of a fibric acid derivative, plasma VLDL and LDL composition and LDL kinetic measurements remained unchanged. By contrast, VLDL triglyceride-apo B decreased and direct LDL synthesis increased in four patients whose phenotype changed to Type IIa. LDL cholesterol/apo B also increased and LDL FCR declined. Among patients with FCHL, significant correlations between VLDL triglyceride/apo B, LDL apo B derived by direct synthesis, LDL cholesterol/apo B, and LDL apo B FCR were found. Thus, increased apo B synthesis is a characteristic feature of FCHL. The phenotypic expression is determined by the availability of triglyceride for hepatic coupling to apo B which could influence the source, composition, and removal rate of circulating LDL. Despite normalization of their plasma lipid levels, some patients continued to show the compositional and kinetic features of FCHL.
Premature development of iliac artery stenosis in asymptomatic type II hyperlipoproteinemia.
Authors: Rubba P , Postiglione A , De Simone B , Faccenda F , Riccardi G , Mancini M
Published: June 2011

There is conflicting evidence on the relationship between increased low density lipoprotein (LDL) concentration in Type II hyperlipoproteinemia and premature development of peripheral atherosclerosis of the lower limbs. We evaluated the early signs of iliac artery involvement in patients with asymptomatic Type II hyperlipoproteinemia. Of these, 23 were Type IIA, 12 were Type IIB. Thirty-five consecutive patients, ages 40 to 60 years, with asymptomatic Type II hyperlipoproteinemia (LDL cholesterol greater than or equal to 3.80 mmol/liter, 147 mg/dl) and 54 normocholesterolemic controls (plasma cholesterol less than 5.70 mmol/liter, 220.6 mg/dl) from a random sample of clinically healthy, 50-year-old men had a noninvasive examination to detect common and external iliac artery stenosis. Both Type II patients and the controls were examined by the echo-Doppler technique (Duplex Scanner III-ATL Mark V) with spectral analysis of the Doppler signals. This method is sensitive not only to severe stenosis or occlusion but also to non-flow-reducing stenosis (less than 50% narrowing of the lumen diameter) and to minor wall irregularities (1%-15% stenosis). In Type II patients, 19 of 70 limbs (27%) were abnormal as compared to 6 of 108 limbs (6%) in the controls (p less than 0.001). The premature development of an obliterating disease of the iliac arteries was demonstrated in persons asymptomatic for Type II hyperlipoproteinemia.
Atherogenic diet-induced modification of the subfraction distribution of high density lipoproteins in monkeys.
Authors: Rudel L L , Nelson C A , Weiss K R
Published: June 2011

High density lipoproteins (HDL) were isolated from the plasma of adult male African green monkeys fed control or atherogenic diets and were then subfractionated in a density gradient by centrifugation at 50,000 rpm, 20 degrees C for 18 hours in the Beckman VTi50 vertical rotor. Material from the gradient was pooled into six subfractions for further analysis. With increasing density across the gradient, the subfractions had progressively decreasing flotation rates, molecular weights, apo A-I/apo A-II mass ratios, lipid percentages of mass, and average sizes. Apoprotein content per particle was reasonably constant compared to lipid content. The physical and chemical properties of the HDL subfractions suggested that the gradient separated three subclasses of HDL equivalent to HDL 2b, HDL 2a, and HDL3 of human beings. When values among animals were compared, the atherogenic diet shifted the relationship between total plasma cholesterol concentration and total HDL concentration from a positive to a negative correlation. The subfractions most affected were those of d less than 1.10 g/ml (HDL2b), while the 1.10 less than d less than 1.13 g/ml (HDL2a) subfractions were affected to a lesser degree; the more responsive the animal to dietary cholesterol, the lower was the mass concentrations of these subfractions. This pattern suggested that diet-induced changes in HDL2 subfraction particle concentrations may be related to the development of atherosclerosis in African green monkeys; parallel changes in particle composition were not identified.
Arterial dermatan sulfate proteoglycan structure in pigeons susceptible to atherosclerosis.
Authors: Rowe H A , Wagner W D
Published: June 2011

Arterial dermatan sulfate proteoglycans (DS-PG) were isolated from randomly bred White Carneau (RBWC) pigeons and a line of White Carneau pigeons (WC-2) genetically selected for increased atherosclerosis susceptibility. To characterize the basic proteoglycan (PG) structure and to identify structural differences that may relate to a specific arterial phenotype, embryos were labeled with radioactive sulfate in ovo and PG were isolated from aortas with 4.0 M GdnHCl. DS-PG were separated from chondroitin sulfate PG by gel chromatography and further purified by CsCl buoyant density ultracentrifugation and ion-exchange of chromatography. The DS-PG monomers from the two genetic lines of pigeons eluted at different positions on two high pressure liquid chromatography (HPLC) gel permeation systems, which suggested a structural difference between the two monomers. Analysis of the monomer components showed a similar protein core molecular weight of 50,000 for each and a similar amino acid composition. Glycosaminoglycans (GAG) molecular weights were estimated to be 15,000 for WC-2 and 18,000 for RBWC. The findings suggest a basic difference in post-translational processing of PG in the two pigeon types which may reflect distinct functional properties associated with resistance or susceptibility to atherosclerosis.
Transmural organization of the arterial media. The lamellar unit revisited.
Authors: Clark J M , Glagov S
Published: June 2011

When scanning electron micrographs of orthogonal transmural fracture surfaces of distended aortas were compared with appearances on corresponding semithin light microscopic and ultrathin transmission electron microscopic sections, medial lamellar units could be resolved into composites of overlapping, musculo-elastic fascicles lying parallel to tangential planes of section. Each fascicle consisted of a group of commonly oriented, elongated smooth muscle cells and an encompassing array of branching, similarly oriented elastic fibers. On longitudinal sections of straight segments of the aorta, fascicles appeared as closely packed, transversely transected smooth muscle cell groups within compartments formed by similarly transected elastic fibers. On transverse sections, fascicles appeared as groups of cells within cell strips or layers, each of which was bracketed on both its luminal and abluminal sides by straight elastic fibers. Fascicles were increasingly evident during growth as commonly oriented groups of cells within the already present concentric cell layers became demarcated by enlarging elastic fibers. Wavy collagen fiber bundles, distinct from the interlaced fibrils of the immediate pericellular matrix, were interposed mainly between the facing elastin systems within the fibrous regions between cell layers. Thus, the radial transmural disposition of cells and matrix fibers on transverse sections of the media in well developed aortas proved to be: elastin-cells-elastin--collagen bundles--elastin-cells-elastin--collagen bundles, etc. Medias of major branch arteries were also composed of musculo-elastic fascicles, but their encompassing elastic fiber systems were less prominent than in the aorta. In straight segments of aortas and arteries, fascicles were uniform in size at any given transmural level and oriented mainly circumferentially. At bends and branch points fascicles were smaller and less uniform in size and orientation. In relation to changes in vessel wall curvature, alignment of the fascicles was usually in the direction of presumed resultant tensile stress. The findings suggest that these subunits of medial organization correspond to the distribution and magnitude of tensile stresses.
Regional compliance of brachial artery and saline infusion in patients with arteriosclerosis obliterans.
Authors: Levenson J A , Simon A C , Maarek B E , Gitelman R J , Fiessinger J N , Safar M E
Published: June 2011

Simultaneous brachial artery pressure and blood flow measurements were made in 15 patients with arteriosclerosis of the lower limbs (AOLL) and in controls of the same age and sex. Blood flow was evaluated by a pulsed Doppler device with a double-transducer probe. From analysis of the pressure-flow curves during diastole, regional arterial compliance (RAC) was determined by using as a model of the forearm arterial tree a system of tubes, each with a storage capacity, in series with the arteriolar resistance vessels. In AOLL patients, RAC was significantly reduced (102 +/- 13 vs 173 +/- 14.10(-4) ml/mm Hg, p less than 0.01), and systolic pressure was significantly increased. After saline infusion, systolic pressure continued to increase and arterial compliance, to decrease; brachial blood flow did not change. Study of the baroreflex sensitivity in AOLL patients under basal conditions indicated that a higher pulse pressure was required to obtain the same heart rate as in the controls. The study provided evidence that in AOLL patients: 1) compliance was reduced in the brachial artery (a regional circulation with no clinical evidence of arterial occlusion); 2) an increase in systolic pressure resulted from the decreased arterial compliance; and 3) saline infusion exaggerated the observed reduction in arterial compliance and increase in systolic pressure.
Epidemiological correlates of high density lipoprotein subfractions, apolipoproteins A-I, A-II, and D, and lecithin cholesterol acyltransferase. Effects of smoking, alcohol, and adiposity.
Authors: Haffner S M , Applebaum-Bowden D , Wahl P W , Hoover J J , Warnick G R , Albers J J , Hazzard W R
Published: June 2011

Recent data suggest that the protection against ischemic heart disease afforded by high density lipoprotein (HDL) cholesterol (C) may be concentrated in the HDL2 subfraction. To examine the behavioral correlates of the HDL subfractions, we recalled 33 men and 17 women of a random sample from the Pacific Northwest Bell Telephone Company Health Survey. Adiposity and very low density lipoprotein (VLDL) triglyceride were negatively correlated with HDL2C. Smoking was not correlated with HDL2C, but was negatively correlated with HDL3C (men, rs = -0.635, p = 0.001; women, rs = -0.534, p = 0.014); this relationship was independent of alcohol consumption, adiposity, and VLDL triglyceride. Alcohol consumption was also more strongly related to HDL3C (men, rs = 0.248, p = 0.082; women, rs = 0.586, p = 0.007). Lecithin cholesterol acyltransferase (LCAT) mass was negatively related with HDL2C, but was positively correlated with HDL3C and apolipoprotein A-II. Smoking was negatively correlated with LCAT mass. Since it is believed that HDL3C is not associated with the risk of ischemic heart disease and since both smoking and alcohol consumption may mainly affect HDL3C, the current study suggests that the increase in risk of ischemic heart disease with smoking and the possible decrease with alcohol consumption may be mediated through mechanisms other than their effects on HDLC.
Ovariectomy, social status, and atherosclerosis in cynomolgus monkeys.
Authors: Adams M R , Kaplan J R , Clarkson T B , Koritnik D R
Published: June 2011

Evidence is contradictory regarding the effects of natural or surgical menopause on "female protection" against coronary artery atherosclerosis. We evaluated atherosclerosis, plasma lipids, blood pressure, and carbohydrate tolerance in 21 ovariectomized and 23 intact female cynomolgus macaques fed a moderately atherogenic diet for 30 months. We also evaluated the influence of social dominance status, with particular emphasis on a possible relationship with ovarian endocrine function. Atherosclerosis was two to 10 times as extensive in coronary, carotid, and iliaco-femoral arteries of the ovariectomized females; this could be explained, in part, by 15% to 20% increases in total plasma and LDL cholesterol concentrations. Socially dominant intact females were protected against advanced atherosclerotic lesions (plaques) of the coronary arteries, while subordinate females and ovariectomized females were not. Increased susceptibility to advanced coronary artery atherosclerosis in subordinate intact females may have been related in some way to chronic ovarian dysfunction observed in seven of 12 of these individuals. As a group, subordinate intact females also had enlarged adrenal glands, suggestive of mechanisms that may influence atherogenesis independently. The results indicate that, in this species, ovariectomy and chronic ovarian dysfunction related to subordinate social status are associated with a more atherogenic plasma lipid pattern and abolish "female protection" against coronary artery atherosclerosis.
Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.
Authors: Sinha A K , Dutta-Roy A K , Chiu H C , Stewart G J , Colman R W
Published: June 2011

Thrombin stimulates prostacyclin formation in cultured human endothelial cells. However, a countervailing process that prevents prostacyclin overproduction has not been described previously. In this study, we demonstrate that Factor Xa can inhibit prostacyclin synthesis induced by thrombin or sodium arachidonate. The required concentration of Factor Xa represents activation of only 2% of the Factor X in plasma. The inhibition is reversed by a human monoclonal antibody directed against the light chain of Factor Va (Mr = 78,000), which suggests that Factor Va is required for this down-regulation of prostacyclin production. Confluent human endothelial cells (10(7)) contained 1.4 to 2.2 micrograms of Factor V antigen as measured by a competitive enzyme-linked immunosorbent assay. The results indicate that in endothelial cells Factor Xa may play a regulatory role in prostacyclin formation through interaction with Factor Va.
Relationship of plasma lipoprotein Lp(a) levels to race and to apolipoprotein B.
Authors: Guyton J R , Dahlen G H , Patsch W , Kautz J A , Gotto A M
Published: June 2011

Lipoprotein Lp(a) is an atherogenic subfraction of plasma lipoproteins which has been studied predominantly in white populations. We quantified Lp(a) by electroimmunoassay in plasma from 105 black and 134 white healthy men and women. Results were correlated with clinical variables and plasma levels of lipids, other lipoproteins, and apolipoprotein (apo) B determined by radioimmunoassay. Black subjects had levels of Lp(a) that averaged twice those of whites (p less than 0.001). Among blacks, Lp(a) levels showed a bell-shaped frequency distribution, while among whites the distribution was strongly skewed, with the highest frequencies at low levels. Contrary to previously published results, the apo B levels in our study correlated significantly, though weakly, with Lp(a) (r = 0.21, p = 0.001 among whites, and r = 0.15, p = 0.02 among blacks, Kendall rank correlation). The regression slopes and variances suggested that apo B in the Lp(a) lipoprotein could account for the correlation. Lp(a) levels did not correlate significantly with any other plasma lipoprotein or lipid levels. The implications of this study are as follows: Despite the high levels of Lp(a) among blacks in the Houston area, these blacks do not experience greatly increased atherosclerotic progression and mortality. Thus, the atherogenicity of Lp(a) in blacks must be decreased or counterbalanced by other factors. The correlation between Lp(a) and apo B should be taken into account when analyzing atherogenic risk, but this correlation is not strong enough to dispute the independence of Lp(a) and apo B as risk factors.
Cholesterol metabolism in juvenile baboons. Influence of infant and juvenile diets.
Authors: Mott G E , Jackson E M , McMahan C A , Farley C M , McGill H C
Published: June 2011

The deferred effects of infant diets and the effects of juvenile diets on cholesterol metabolism were estimated in 83 baboons (Papio sp.) at 3.5 years of age. As infants, the animals were breast-fed or fed one of three formulas containing approximately 2, 30, or 60 mg/dl cholesterol. After weaning at 14 weeks of age, the animals were fed one of four juvenile diets high or low in cholesterol with saturated (P/S = 0.37) or unsaturated (P/S = 2.1) fats. Cholesterol absorption and cholesterol turnover were measured by fecal isotopic methods, and variables of cholesterol metabolism were estimated from a two-pool model. Among juvenile animals breast-fed during infancy, the percentage of cholesterol absorption was higher, while the fluxes of cholesterol from Pool A (QAA, QA, and QAB) and the cholesterol mass of Pool B were lower, compared to those fed formulas. The level of cholesterol in formulas fed during infancy did not influence cholesterol metabolism during the juvenile period. During the juvenile period, saturated fat significantly decreased the cholesterol production rate (QA) and increased the rate constants for cholesterol flux between Pool A and Pool B (KAB and KBA) compared to unsaturated fat. High cholesterol intake increased bile acid and neutral steroid excretion, cholesterol turnover rate, the mass of Pool A, and the rate constant KA and fluxes QA and QAA for removal of cholesterol from Pool A. However, KAB, t1/2 B (half-time of Pool B), and the percentage of cholesterol absorbed were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetic mechanisms determining variability in low density lipoprotein levels and rise with age.
Authors: Grundy S M , Vega G L , Bilheimer D W
Published: June 2011

Levels of plasma low density lipoproteins (LDL) vary among individuals at any given age and frequently rise with increasing age. Both production rates and fractional clearance rates (FCRs) of LDL theoretically could affect the plasma levels of LDL. To evaluate the relative importance of these two factors, turnover rates of LDL apoprotein (apoLDL) were determined in two groups: 19 young adult men aged 23 to 29 years and 15 middle-aged men aged 40 to 60 years. Results were compared to a group of six healthy young adults (aged 22 to 28 years) who we previously studied and who were on a cholesterol-lowering diet. In both groups in the current study, a diet resembling the average American diet was consumed, and LDL levels ranged from low-to-high normal. On average, the 19 young adult men had lower levels of total cholesterol and LDL cholesterol than did the middle-aged men. The younger men also had significantly higher FCRs and lower production rates of apoLDL. When data from all subjects were pooled, apoLDL levels were negatively and significantly correlated with FCRs and positively and significantly correlated with production rates. Similar relations were found with LDL cholesterol levels. These results show that both FCRs and production rates of apoLDL are important regulators of plasma LDL levels; the correlation suggests that the FCR is more influential at lower LDL concentrations, and that production rates are more influential at higher LDL concentrations.
Effects of fenofibrate on bile lipid composition.
Authors: Palmer R H
Published: June 2011

In humans, clofibrate increases the degree of bile cholesterol saturation and predisposes patients to cholesterol gallstone formation. To determine if this activity extends to the related hypolipidemic agent fenofibrate, duodenal bile lipid composition was studied in 15 subjects before they participated in a double-blind study of that drug. Eight subjects were studied again on fenofibrate and six on placebo; five placebo patients were also studied later on open-label fenofibrate. The results were similar in the double-blind and open-label studies, and changes in bile lipid composition were comparable to those seen in studies of clofibrate. Fenofibrate caused a significant decrease in the molar percentage of bile acids and increases in the molar percentage of phospholipids and cholesterol. The changes in bile acids and phospholipids had opposing effects on the cholesterol-holding capacity of bile. A statistically significant increase in the cholesterol saturation index was only apparent when all fenofibrate bile analyses were compared with all untreated bile analyses. The results demonstrated that fenofibrate has clear effects on bile lipid composition that may be associated with an increased propensity for gallstone formation, and when fenofibrate is used, patients should be monitored for this possibility.
Apo E allele frequency in primary endogenous hypertriglyceridemia (type IV) with and without hyperapobetalipoproteinemia.
Authors: Lussier-Cacan S , Bouthillier D , Davignon J
Published: June 2011

Apolipoprotein E polymorphism is responsible for the existence in the population of six apo E phenotypes determined by three alleles acting at a single gene locus. We have previously reported an enrichment in the epsilon 2 allele and the E2-bearing phenotypes in an unselected sample of subjects with primary hyperlipidemia consisting mainly of endogenous hypertriglyceridemia (Type IV). A study was carried out on 214 Type IV hypertriglyceridemic subjects to determine whether there was the same distribution in subjects with hyperapobetalipoproteinemia as in those without. The study showed that the relative enrichment in the epsilon 2 allele was associated only with Type IV subjects without hyperapobetalipoproteinemia. Since hyperapobetalipoproteinemia is a presumed marker for familial combined hyperlipidemia (FCHL), this finding may provide further evidence that FCHL and familial hypertriglyceridemia, both associated with a Type IV lipoprotein pattern, are truly separate disease entities.
Androgen directs apparent cytoplasmic and nuclear distribution of rat cardiovascular androgen receptors.
Authors: Lin A L , Gonzalez R , Shain S A
Published: June 2011

We used either the synthetic androgen R1881 (methyltrienolone) or 5 alpha-dihydrotestosterone (5 alpha-DHT) to characterize androgen receptors in rat aortic and myocardial cytoplasmic and nuclear preparations. Relative steroid specificity studies established that only androgens were effective inhibitors of R1881 (cytoplasmic) or 5 alpha-DHT (nuclear) binding to aortic and myocardial androgen receptors, whereas estrogens, progestins, and cortisol were ineffective inhibitors. Low ionic strength sucrose density gradient centrifugation analyses showed that androgen receptors in aortic and myocardial cytoplasmic preparations migrated as macromolecules with sedimentation coefficients of 8 to 9S, whereas androgen receptors in aortic and myocardial nuclear preparations migrated as macromolecules with sedimentation coefficients of 4 to 5S (high ionic strength buffer). Saturation analyses established that aortic and myocardial cytoplasmic preparations from intact, untreated young mature female rats contained 45.8 +/- 9.7 (mean +/- SD) and 63.3 +/- 20.7 fmol androgen receptor/mg DNA, respectively. The respective R1881 dissociation constants were 0.60 and 0.32 nM. Androgen receptors could not be demonstrated in nuclear preparations from the cardiovasculature of intact females. Testosterone injection of intact young mature female rats caused apparent depletion of androgen receptors in aortic and myocardial cytoplasmic preparations and resulted in concomitant appearance of 57.1 +/- 22.2 and 52.3 +/- 21.5 fmol receptor/mg DNA in the corresponding nuclear preparations. The respective 5 alpha-DHT dissociation constants were 4.46 and 1.63 nM. The ability of testosterone to affect apparent intracellular distribution of cardiovascular androgen receptors suggests that the receptors are physiologically functional and indicates that androgen may directly regulate cardiovascular cell function.
Risk factors for changes in aorto-iliac arterial compliance in healthy men.
Authors: Relf I R , Lo C S , Myers K A , Wahlqvist M L
Published: June 2011

Doppler ultrasound was used to measure pulse wave velocity down the aorta and iliac arteries. Arterial wall compliance was calculated from pulse wave velocity in 45 apparently healthy men. Their arterial compliance fell significantly with advancing age, raised blood pressure, increased serum cholesterol and triglyceride levels, and reduced serum high density lipoprotein cholesterol levels. The correlation between compliance and age was independent of the other risk factors, and the correlation between compliance and lipid status was independent of age and blood pressure. There was no significant correlation between compliance and area under the glucose tolerance curve.
Distribution of the geometric parameters of human aortic bifurcations.
Authors: Bargeron C B , Hutchins G M , Moore G W , Deters O J , Mark F F , Friedman M H
Published: June 2011

The distribution of flow divider offset, branch angle, and angular asymmetry in a collection of 70 human aortic bifurcations are reported. A computer algorithm was used to determine these parameters objectively. The mean values with standard deviations and ranges are: 1) magnitude of flow divider offset = 1.4 +/- 1.4 mm (range = 0.04 to 8.1 mm); 2) branch angle = 35.0 degrees +/- 11.1 degrees (range = 10.4 degrees to 61.3 degrees); and 3) angular asymmetry = 15.3 degrees +/- 12.9 degrees (range 0.2 degrees to 56.1 degrees). Since these parameters have been shown to have a significant influence on hemodynamic shear, their variability suggests a corresponding variability in the fluid dynamic stresses to which the bifurcations were exposed in life.
Influx, efflux, and hydrolysis of cholesteryl ester in atheromatous lesions of cholesterol-fed rabbits.
Authors: Hough J L , Zilversmit D B
Published: June 2011

Total plasma lipoproteins were labeled with radioactive cholesteryl ester or cholesteryl ether by transfer of these lipids from phosphatidylcholine vesicles in the presence of plasma lipid transfer activity. Intravenous injection of these preparations into hypercholesterolemic rabbits showed disappearance curves identical to those of in vivo labeled lipoproteins. Disappearance of cholesteryl ester and ether were similar during the first 24 hours, but they diverged at later time intervals, indicating recirculation of labeled cholesteryl ester. Lipoproteins labeled with cholesteryl ether were injected at 25 days, 7 days and 1 day before sacrifice of the rabbits. The maximal loss of labeled ether from the aortas during a 24-hour period ranged from 1.6% to 8.9% of the labeled ether taken up from plasma. Hydrolysis of cholesteryl ester by the artery during 24 hours averaged 35% of the calculated cholesteryl ester influx. After hydrolysis, cholesteryl ester fatty acid appeared to be esterified more rapidly than the cholesterol moiety of the cholesteryl ester.
Effect of 17 beta estradiol on aortic cholesterol content and metabolism in cholesterol-fed rabbits.
Authors: Hough J L , Zilversmit D B
Published: June 2011

Administration of estrogen to cholesterol-fed rabbits dramatically retarded arterial lesion development despite its lack of effect on plasma cholesterol concentration and on lipoprotein patterns. Cholesteryl ester influx into the aortic wall was also much lower in the estrogen-treated animals and paralleled the aortic cholesterol content in treated and untreated animals; the fraction of aortic cholesteryl ester lost by efflux was the same in treated and untreated animals. The fraction of newly entered cholesteryl ester hydrolyzed by aorta was significantly reduced in the estrogen-treated animals. Low cholesteryl ester influx and relatively less hydrolysis of cholesteryl ester by the aorta may be indicative of reduced internalization of plasma cholesteryl ester by aortic cells, which may in turn account for the reduced atherogenesis in the estrogen-treated rabbits.
Induction of increased collagen and elastin biosynthesis in copper-deficient pig aorta.
Authors: Hill K E , Davidson J M
Published: June 2011

Young pigs raised on a copper-deficient diet develop severe abnormalities of connective tissue due to defective cross-linking of collagen and elastin. They eventually succumb to anemia and cardiovascular damage, the latter apparently due to the defective connective tissue metabolism. We evaluated the effects of nutritional copper deficiency upon collagen and elastin synthesis using short-term explant cultures of the medial portion of four successive segments of the descending aorta from 110-day-old pigs raised on a copper-deficient diet. Collagen synthesis was evaluated by collagenase susceptibility, and elastin synthesis was quantified by immunoprecipitation with an antiporcine-elastin antiserum. In the normal developing aorta, elastin synthesis was maximal in the upper thoracic aorta, while levels of collagen synthesis were highest in the lower abdominal aorta. Both activities subsided by 110 days postpartum. Compared with controls, the copper-deficient group showed: 1) histopathologic changes confined to the luminal half of the thoracic aorta; 2) a 1.3- to 1.6-fold increase in cellularity along the entire length of the organ; 3) a 1.3- to 2.4-fold increase in relative collagen synthesis, the greatest change occurring in the thoracic portion; 4) a 3- to 4-fold increase of relative elastin synthesis in the thoracic aorta, the abdominal aorta remaining unchanged; 5) 4- to 10-fold increases in collagen production; and 6) a greater than 15-fold increase in elastin production by the tissue of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
The mechanism of fibrin-induced disorganization of cultured human endothelial cell monolayers.
Authors: Weimar B , Delvos U
Published: June 2011

Deposition of polymerizing fibrin on the vascular endothelium is the final event in intravascular coagulation. Exposure of fibrin clots to confluent monolayers of cultured human endothelial cells for 4 to 24 hours resulted in the disappearance of their normal cobblestone morphology and in the formation of endothelial cell aggregates. The present study was designed to evaluate the conditions and structural requirements of the fibrin clot for the induction of disorganization. Even after harsh treatment with denaturing agents or loading with large amounts of fibrinogen antibodies, polymerized fibrin always induced disorganization of the monolayers. In contrast, soluble fibrin that was kept in solution by either fibrinogen, fragment D-cate, or the tetrapeptide Gly-Pro-Arg-Pro did not cause any alteration of the monolayers. The fibrinogen degradation product D-cate (Mr 94,000) itself had no microscopically detectable influence on the monolayer structure. In the absence of fibrin, the effect of thrombin on endothelial cells was found to be distinct from that induced by fibrin; however, the exposure of pieces of glass coverslips caused alterations in morphology indistinguishable from the fibrin-induced disorganization of the monolayer. Experiments using protein-coated polyester films indicated that the ability of the endothelial cells to attach to the overlying material, independent of its chemical structure, is the prerequisite for the induction of disorganization, but not a defined component of the fibrin molecule. Disorganization of vascular endothelium in vivo might be important for the organization and revascularization of an occluding thrombus.
Improved arterial distensibility in normotensive subjects on a low salt diet.
Authors: Avolio A P , Clyde K M , Beard T C , Cooke H M , Ho K K , O'Rourke M F
Published: June 2011

Arterial pulse wave velocity (PWV), a noninvasive index of arterial distensibility, was measured in 57 normotensive subjects who followed a voluntary low salt diet for a period ranging from 8 months to 5 years (mean, 24.8 months). Subjects who followed a regular diet were matched for age and mean arterial pressure with the low salt (LS) sample and were used as controls (C). For both samples, subjects were divided into three age groups: Group 1 (aged 2 to 19 years, n = 16), Group 2 (29 to 44 years, n = 26), and Group 3 (45 to 66 years, n = 15). There was a marked increase in aortic PWV with age in the control sample but not in the LS sample. There was no significant difference in aortic PWV for Group 1, but in Groups 2 and 3, the LS subjects showed a decrease of 21.8% and 22.7%, respectively, compared to C subjects. Aortic PWV (cm/sec) was: Group 1: C = 581 (SE44), LS = 614 (SE31); Group 2: C = 942 (SE46); LS = 737 (SE27) (p less than 0.001); Group 3: C = 958 (SE77), LS = 741 (SE25) (p less than 0.05]. Arm and leg PWV were also significantly lower in the older age groups. These findings suggest that normotensive adult subjects who follow a low salt diet (mean intake, 44 mmol Na/24 hours) have reduced arterial stiffness and that the effect is independent of blood pressure. This is prima facie evidence that reduced salt intake has a beneficial effect in improving distensibility of the central aorta and large peripheral arteries, which is independent of its antihypertensive action.
Arteriosclerosis in Atlantic salmon. Effects of dietary cholesterol and maturation.
Authors: Farrell A P , Saunders R L , Freeman H C , Mommsen T P
Published: June 2011

Coronary arteriosclerosis was examined in cultured Atlantic salmon (Salmo salar L.) maintained on normal and cholesterol-enriched diets in both freshwater and saltwater during the period when they normally mature (June to December). The incidence of lesions was high (48% or greater) in all experimental subgroups (assigned according to diet, salinity, sex, and maturation status). The primary factor in the development of arteriosclerotic lesions was not established, but the high frequency of lesions in immature fish suggests that it was not maturation. However, maturation was associated with a significant increase in the incidence of lesions and was, therefore, an important secondary factor in the etiology of the disease. Furthermore, diet had a secondary influence on the development of lesions since the cholesterol supplement was also associated with an increase in the incidence of lesions. The cholesterol supplement significantly increased the total plasma cholesterol level in all subgroups; the low density lipoprotein fraction (total cholesterol minus the high density lipoprotein fraction) was also elevated in seven of eight paired subgroups. Plasma free fatty acids and triglycerides were unaffected by the cholesterol supplement. The elevated total cholesterol and low density lipoprotein levels resulting from the cholesterol-enriched diet and the associated increase in the incidence of lesions was most prominent in mature males and females held in freshwater. Salinity had no demonstrable effect on lesion incidence, but the severity of lesions tended to be greater in freshwater fish.
Uptake of low density lipoprotein, albumin, and water by deendothelialized in vitro minipig aorta.
Authors: Fry D L , Cornhill J F , Sharma H , Pap J M , Mitschelen J
Published: June 2011

The purpose of this research was to study the effect of pressure on arterial hydration in vitro and the effect of pressure and flow (stirred reagent) on the in vitro transport of 125I-albumin and 125I-LDL into deendothelialized minipig aortas over a 24-hour period. It was found that the arterial hydration (fractional mass of water) was 0.740 +/- 0.0043 SEM for control tissue; after 24 hours this rose to 0.745 +/- 0.0038 for 0 mm Hg, 0.752 +/- 0.0046 for 100 mm Hg, and 0.755 +/- 0.0065 for 200 mm Hg. In the transport studies, the following effects were found. The reagent radioactivity concentration and composition did not change with pressure or stirring over the 24-hour period. For unpressurized tissue, the 24-hour normalized uptake [uptake (M mg cm-2) divided by reagent concentration (co mg cm-3)] of albumin was (4.86 +/- 0.43 cm) X 10(-3) from stirred and (5.46 +/- 0.36 cm) X 10(-3) from nonstirred reagent; that of LDL was (0.31 +/- 0.02 cm) X 10(-3) from stirred and (0.37 +/- 0.02 cm) X 10(-3) from nonstirred reagent. Pressurization (100 mm Hg) of the tissue increased albumin uptake by 52% from stirred and by 125% from nonstirred reagent and the LDL uptake by 52% from stirred and 241% from nonstirred reagent. Pressure increased the intimal surface concentration of albumin and LDL at the nonstirred, but not at stirred, interfaces. The electrophoretic properties of the intimal surface fluid showed only minor differences from those of the bulk reagent. These data demonstrate that pressure causes a slight, but significant, increase in arterial hydration and that radiolabeled albumin and LDL appear to be sieved by the superficial intimal layers of the deendothelialized porcine aorta under the in vitro conditions of this study.
Effects of fenofibrate on plasma lipids. Double-blind, multicenter study in patients with type IIA or IIB hyperlipidemia.
Authors: Brown W V , Dujovne C A , Farquhar J W , Feldman E B , Grundy S M , Knopp R H , Lasser N L , Mellies M J , Palmer R H , Samuel P
Published: June 2011

Of 240 patients with Type IIa and IIb hypercholesterolemia recruited in 11 centers, 227 were randomized to double-blind treatment with either fenofibrate (100 mg three times daily) or matching placebo for 24 weeks. A group of 192 of these patients were studied for a further 24 weeks during which all received fenofibrate in open label fashion. For the 92 Type IIa patients receiving fenofibrate in the double-blind phase, there were significant reductions (p less than 0.01 compared to baseline) in total plasma cholesterol (-18%), LDL-cholesterol (-20%), VLDL-cholesterol (-38%) and total triglycerides (-38%). Mean plasma HDL-cholesterol in these patients increased by 11% (p less than 0.01). With the exception of LDL, which was not high before treatment, similar changes were seen in the 24 fenofibrate-treated Type IIb subjects. Lipid parameters of placebo-treated patients did not change significantly. This pattern of change was repeated in the open period for the 94 patients previously on placebo, while the 98 who had been on fenofibrate remained stable with small further reductions in total and LDL cholesterol (-38% and -5.5% respectively). Adverse effects were some allergic-type skin reactions early in treatment and an occasional increase in transaminases, BUN, or creatinine. The results were similar to those obtained in European open trials of fenofibrate and were better than the lipid changes seen at comparable times in the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) cholestyramine study.
Influence of dietary fats on blood coagulation and prostaglandin production in the common marmoset.
Authors: McIntosh G H , McMurchie E J , James M , Lawson C A , Bulman F H , Charnock J S
Published: June 2011

Common marmosets were fed a standard marmoset diet (REF) or diets supplemented with 12% (wt/wt) sunflower seed oil (SSO) or sheep fat (SF) for a period of 90 weeks. The values for coagulation indices, clotting time, and Russel viper venom time were consistent with decreased thrombotic tendency of platelets from animals on the SSO diet relative to the low fat, REF diet animals, while an increased tendency to thrombosis was observed with SF-fed marmosets. The SSO- and SF-supplemented marmosets showed a significantly reduced thromboxane (TXB2) generation from platelets aggregating to collagen (ASC) relative to the REF group, while at 50 micrograms/ml ASC this difference was maintained only by the SSO group. The SF diet-fed marmosets showed a reduced prostacyclin (measured as 6-keto-PGF1 alpha) generation from incubated aorta relative to the REF or SSO-fed groups, which were not different from each other. A reduced proportion of platelet phospholipid arachidonic acid (20:4, n-6) and increased alpha-tocopherol concentration was consistent with the decreased aggregability and thromboxane generation of platelets from SSO-fed marmosets relative to the REF and SF groups. The SF diet-fed marmosets, on the other hand, showed minimal change in arachidonic acid, alpha-tocopherol or platelet reactivity from the REF group. These differing responses to dietary fats are discussed in relation to the potential for the development of thrombosis and atherosclerosis.
Hyperapobetalipoproteinemia in a kindred with familial combined hyperlipidemia and familial hypercholesterolemia.
Authors: Kwiterovich P O , White S , Forte T , Bachorik P S , Smith H , Sniderman A
Published: June 2011

A child showed a type IIb lipoprotein pattern and triglyceride-enriched cutaneous xanthomas before 1 year of age. The proband and 9 of 18 relatives had elevated plasma levels of low density lipoprotein (LDL) B protein; of these nine relatives, four had elevated LDL of increased density while five had elevated LDL of normal density. Compared with normal LDL, LDL of increased density had less cholesteryl ester and free cholesterol, more apolipoprotein B and triglyceride, and a lower molecular weight and flotation rate (Sf degrees). Patients with LDL of increased density had higher mean plasma levels of triglycerides, very low density lipoproteins, and intermediate density lipoproteins, but lower levels of high density lipoproteins than those with elevated LDL of normal density. Multiple lipoprotein patterns in the father's family suggested the presence of familial combined hyperlipidemia (FCH). The mother of the proband and two of her relatives had type IIa lipoprotein patterns and tendon xanthomas, compatible with familial hypercholesterolemia (FH). High affinity binding, internalization, and degradation of 125I LDL in cultured fibroblasts from the proband and his mother were reduced two- to threefold compared with normal cells, while LDL receptor activity in the proband's father was normal. This unusual proband has apparently inherited both FCH and FH.