Showing papers on "High-density lipoprotein published in 1994"

Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse

Abstract: Atherosclerosis is a complex disease with both genetic and environmental determinants. Apolipoprotein (Apo) E-deficient mice have been created that are highly susceptible to atherosclerosis. In order to assess the role of human apolipoprotein (hApo) A-I and high density lipoprotein (HDL) in atherosclerosis susceptibility, transgenic mice overexpressing the hApo A-I gene were crossed with Apo E-deficient mice. Apo E-/-, hApo A-I mice with two-fold elevation in HDL cholesterol have markedly diminished atherosclerosis with less fibroproliferative lesions by 8 months of age. A strong reciprocal relationship between HDL cholesterol levels and atherosclerosis was found with HDL levels accounting for 78% of the observed variance in mean lesion area. The effect of HDL on atherosclerosis resistance was independent of non-HDL cholesterol.

Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study.

Abstract: Objective: To estimate the influence of plasma total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease. Design: The Copenhagen city heart study is a prospective observational survey with two cardiovascular examinations at five year intervals. Non- fasting plasma lipids were measured in participants once at each examination, along with other variables. The Cox regression model was used to establish the effect of the factors recorded on cerebrovascular events of mostly, but not exclusively, ischaemic origin. Subjects — 19 698 women and men at least 20 years old, randomly selected after age stratification from an area of central Copenhagen. Main outcome measures: Initial cases of stroke and transient ischaemic attack recorded from hospital records and death certificates from 1976 through 1988. Results: 660 non-haemorrhagic and 33 haemorrhagic events were recorded. Total cholesterol was positively associated with risk of non-haemorrhagic events, but only for levels >8 mmol/l, correspaonding to the upper 5% of the distribution in the study population. For lower plasma cholesterol values the relative risk remained nearly constant. Plasma triglyceride concentration was significantly, positively associated with risk of non- haemorrhagic events. The relative risk corresponding to an increase of 1 mmol/l was 1.12 (95% confidence interval 1.07 to 1.16). There was a negative, log linear association between high density lipoprotein cholesterol and risk of non-haemorrhagic events (0.53 (0.34 to 0.83)). There was no indication that the20effects of plasma lipids were different in women and men. Conclusions: The pattern of the association between plasma cholesterol and risk of ischaemic cerebrovascular disease was not log linear, and the increased risk was confined to the upper 5% of the cholesterol distribution. Further studies should concentrate on the association between plasma cholesterol and varified haemorrhagic stroke.

Oat beta-glucan reduces blood cholesterol concentration in hypercholesterolemic subjects.

Abstract: Objective Several studies have indicated that consumption of oat bran lowers blood cholesterol and this effect has been attributed specifically to oat bran's soluble fiber (beta-glucan). This study was designed to test this hypothesis. Design The purified fibre (oat gum, 80% beta-glucan) was isolated, and agglomerated in the presence of maltodextrin to facilitate dispersion in a drink. Subjects consumed the oat gum (2.9 g beta-glucan), or maltodextrin placebo, twice daily for 4 weeks, in a randomized, cross-over design with a 3 week wash-out between phases. Consumption was equivalent to a daily dose of about 70 g of oat bran. Setting The study was with free-living individuals. Subjects Twenty hypercholesterolemic male and female adults entered, and 19 completed, the study. Interventions Blood lipids from fasting individuals were measured weekly throughout the study. Diet was monitored using 3 day food diaries. Results There were no significant changes (P > 0.05) in blood lipids during the placebo phase. Mean initial total cholesterol (6.76 +/- 0.13 mmol/l) and low density lipoprotein (LDL) cholesterol (4.59 +/- 0.14 mmol/l) levels fell throughout the oat gum phase, and at week 4 each was reduced 9% relative to initial values (P = 0.0004 and 0.005 respectively). When oat gum was discontinued, total and LDL cholesterol returned to initial levels. There were no significant changes in high density lipoprotein (HDL) cholesterol. Triglyceride levels also remained unchanged except for a singular decrease at week 4 of the oat gum phase relative to the initial value, but not compared to the placebo value. The lowered mean total and LDL cholesterol levels occurred in the absence of any dietary changes. Conclusions The main component of the soluble fibre of oats, beta-glucan, significantly reduced the total and LDL cholesterol levels of hypercholesterolemic adults without changing HDL cholesterol.

Hyperuricemia and insulin resistance.

Abstract: The associates of gout-obesity, hypertriglyceridemia, glucose intolerance, and hypertension, strikingly resemble those of insulin resistance. In the present study we determined whether hyperuricemia is associated with insulin resistance and, if so, whether this association can be explained by other components of the syndrome. For this purpose we quantitated insulin sensitivity (euglycemic clamp) in 37 nondiabetic subjects (aged 30-68 yr) exhibiting varying degrees of the metabolic syndrome (body mass index, 21.5-35.7 kg/m2; serum triglycerides, 0.4-22.0 mmol/L; high density lipoprotein cholesterol 0.38-1.86 mmol/L; blood pressure, 190-100/116-60 mm Hg). In simple linear regression analysis, the serum uric acid concentration (range, 182-568 mumol/L) was inversely correlated with insulin sensitivity (rate of glucose utilization; r = -0.61; P < 0.001) and positively with serum triglycerides (r = 0.68; P < 0.001), but not with body mass index, age, or the plasma glucose concentration. In multiple linear regre...

Effect of adiposity on plasma-lipid transfer protein activities - a possible link between insulin-resistance and high-density-lipoprotein metabolism

Abstract: The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index >27 kg m(-2)) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P It is concluded that the activities of CETP and PLTP are influenced by adiposity and possibly by insulin resistance. Elevated lipid transfer protein activities may provide a mechanism that contributes to alterations in HDL in insulin resistant states.

High-density lipoprotein cholesterol and premature coronary heart disease in urban Japanese men.

Abstract: BACKGROUND The objective of this study was to examine the relation of high-density lipoprotein cholesterol (HDL-C) to coronary heart disease in Japanese men whose serum total cholesterol is low by Western standards. METHODS AND RESULTS A prospective, observational study based on 7.7 years of follow-up for incidence of coronary heart disease and stroke was conducted. The subjects were 6408 middle-aged male workers aged 40 to 59 years at baseline in urban companies in Osaka, Japan, whose mean serum total cholesterol was 5.10 mmol/L. Mean HDL-C adjusted for age, total cholesterol, systolic blood pressure, alcohol intake, cigarette smoking, and body mass index was 1.27 to 1.28 mmol/L for men who developed coronary heart disease (n = 46) or definite myocardial infarction (n = 21) compared with 1.46 mmol/L for those free of cardiovascular disease (n = 6256; difference, P or = 1.66 mmol/L), and there was a significant dose response for definite myocardial infarction. Serum total cholesterol was positively and significantly associated with coronary heart disease incidence. Furthermore, the inverse association for HDL-C was apparent among men with total cholesterol or = 5.69 mmol/L (mean total cholesterol, 6.26 mmol/L). CONCLUSIONS Coronary heart disease incidence is inversely related to HDL-C in urban Japanese middle-aged men, whose mean total cholesterol (5.10 mmol/L) is relatively low.

Tracking and Predictiveness of Serum Lipid and Lipoprotein Measurements in Childhood: A 12-year Follow-up The Cardiovascular Risk in Young Finns Study

Abstract: The authors analyzed tracking and predictiveness of serum lipid and lipoprotein measurements in Finnish children and young adults over a 12-year follow-up period. A representative sample of 3,596 healthy subjects aged 3-18 years was examined in 1980. The follow-up studies were done in 1983, 1986, 1989, and 1992. Data were available on serum lipids and lipoproteins, anthropometric measurements, dietary and smoking habits, and use of oral contraceptives. Complete data on serum lipids in 1980 and 1992 were available for 883 subjects (47% males), and they comprised the study cohort for this analysis. Significant tracking was found in each of the serum lipid variables studied. The range of 12-year correlations was 0.48-0.58, 0.53-0.58, 0.53-0.58, 0.57-0.59, and 0.33-0.37 for serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, the LDL:HDL cholesterol ratio, and triglycerides, respectively. Males showed more tracking than females; there was no clear age trend. Tracking of HDL2 cholesterol was better than that of HDL3 cholesterol (0.64 vs. 0.43, respectively; 3-year tracking). Apolipoproteins A-I and B showed similar amounts of tracking compared with HDL and LDL cholesterol, respectively. Approximately 50% of subjects who initially fell into the extreme quintiles of total cholesterol, LDL cholesterol, and HDL cholesterol were in the same quintiles after 12 years. In multiple regression analyses, childhood obesity, exercise, diet, and smoking habits did not markedly aid the prediction of adult serum lipid values. However, the use of two childhood measurements increased the amount of adult serum lipid variability explained. Although universal screening cannot be endorsed, these findings emphasize the importance of serum lipid measurements in the early detection of familial lipoprotein disorders and in the initial evaluation of coronary heart disease risk in childhood.

Cholesterol content in tumor tissues is inversely associated with high-density lipoprotein cholesterol in serum in patients with gastrointestinal cancer.

Abstract: Background. The authors have previously demonstrated in different experimental models that sustained processes of cellular growth are characterized by alterations of cholesterol metabolism not only in the proliferating tissues but also in the plasma compartment. Methods. To evaluate whether alterations of cholesterol metabolism similar to those observed in experimental models are also associated with human cancer, in the present study cholesterol distribution in tumor tissues and lipid composition in the plasma compartment were determined in patients with different types ofgastrointestinal cancer. Results. The results showed that tumor tissues contain increased amounts of cholesterol when compared with the corresponding normal tissues. Intracellular alterations of cholesterol were accompanied by specific changes of cholesterol in the plasma compartment: highdensity lipoprotein (HDL) cholesterol was markedly reduced in the serum of patients with gastrointestinal cancer and the lipoprotein profiles showed a decrease in HDL, fraction, the main HDL subfraction in human serum. The decrease of HDL cholesterol was negatively associated with the clinical stage of the disease. No changes in either total or low-density lipoprotein cholesterol levels were observed.

Higher plasma lipid transfer protein activities and unfavorable lipoprotein changes in cigarette-smoking men.

Abstract: The mechanism responsible for the atherogenic lipoprotein changes associated with cigarette smoking are largely unknown. Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of plasma cholesterol and the transfer of cholesteryl ester from high-density lipoproteins (HDLs) toward very-low- and low-density lipoproteins (VLDLs+LDLs). Another transfer factor, phospholipid transfer protein (PLTP), recently has been shown to be involved in the interconversion of HDL particles in vitro, but its physiological function is not yet clear. We measured the activities of LCAT, CETP (as cholesteryl ester exchange activity), and PLTP using exogenous substrate assays as well as lipoprotein profiles in the plasma of 21 normolipidemic cigarette-smoking men (total plasma cholesterol below 6.5 mmol/L and triglyceride below 2.5 mmol/L) and 21 individually matched nonsmoking control subjects. HDL cholesterol, HDL cholesteryl ester, and plasma apolipoprotein A-I levels were lower in the smokers than in the control subjects (P < or = .05 for all parameters). Median plasma CETP activity was 18% higher (P < .02) and median plasma PLTP activity was 8% higher (P < .05) in the smokers compared with the nonsmokers. LCAT activity was not different between the groups. HDL cholesteryl ester concentration was positively related to LCAT activity in control subjects but not in smokers. By contrast, there was an inverse relation of CETP activity with HDL cholesteryl ester in smokers but not in nonsmokers. Multiple regression analysis demonstrated that the lowering effect of smoking on HDL cholesteryl ester could be explained by its influence on CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

Abstract: Classic (complete) lecithin:cholesterol acyltransferase (LCAT) deficiency and Fish-eye disease (partial LCAT deficiency) are genetic syndromes associated with markedly decreased plasma levels of high density lipoprotein (HDL) cholesterol but not with an increased risk of atherosclerotic cardiovascular disease. We investigated the metabolism of the HDL apolipoproteins (apo) apoA-I and apoA-II in a total of five patients with LCAT deficiency, one with classic LCAT deficiency and four with Fish-eye disease. Plasma levels of apoA-II were decreased to a proportionately greater extent (23% of normal) than apoA-I (30% of normal). In addition, plasma concentrations of HDL particles containing both apoA-I and apoA-II (LpA-I:A-II) were much lower (18% of normal) than those of particles containing only apoA-I (LpA-I) (51% of normal). The metabolic basis for the low levels of apoA-II and LpA-I:A-II was investigated in all five patients using both exogenous radiotracer and endogenous stable isotope labeling techniques. The mean plasma residence time of apoA-I was decreased at 2.08 +/- 0.27 d (controls 4.74 +/- 0.65 days); however, the residence time of apoA-II was even shorter at 1.66 +/- 0.24 d (controls 5.25 +/- 0.61 d). In addition, the catabolism of apoA-I in LpA-I:A-II was substantially faster than that of apoA-I in LpA-I. In summary, genetic syndromes of either complete or partial LCAT deficiency result in low levels of HDL through preferential hypercatabolism of apoA-II and HDL particles containing apoA-II. Because LpA-I has been proposed to be more protective than LpA-I:A-II against atherosclerosis, this selective effect on the metabolism of LpA-I:A-II may provide a potential explanation why patients with classic LCAT deficiency and Fish-eye disease are not at increased risk for premature atherosclerosis despite markedly decreased levels of HDL cholesterol and apoA-I.

Physiological Levels of Estradiol Stimulate Plasma High Density Lipoprotein2 Cholesterol Levels in Normal Men

Abstract: Premenopausal women have a lower risk of coronary artery disease than men or postmenopausal women; estrogens are thought to contribute to this lower risk. Administration of exogenous estrogen to post-menopausal women increases plasma high density lipoprotein (HDL) cholesterol and may reduce mortality from coronary disease in users. Although many investigations have examined the roles of estrogen in the regulation of lipoproteins in women, little attention has been directed to estrogen regulation of lipids in men. We designed a paradigm to study the role of physiological levels of estradiol (E2) on plasma lipoproteins in healthy men. We used a GnRH antagonist, Nal-Glu, to suppress endogenous steroid hormones in healthy men. We then administered testosterone (T) enanthate (100 mg, im, weekly) to restore T levels to the baseline range, and we administered an aromatase inhibitor, testolactone (Teslac), to prevent the normal conversion of T to E2, thereby producing a selective estrogen deficiency state in normal young men. As controls, we administered Nal-Glu and T along with placebo Teslac to a separate group of men; a third group of men received all placebo medications. We found that in men who received Nal-Glu plus T plus Teslac, E2 levels were profoundly suppressed during treatment, whereas T levels remained in the baseline range. Plasma HDL cholesterol, particularly, the HDL2 fraction, decreased significantly in response to the low serum E2 level. Plasma apoprotein-AI levels also decreased significantly. Plasma LDL and triglyceride levels did not change. All hormone and lipoprotein parameters returned to baseline within 4 weeks after treatment ended. In men who received Nal-Glu plus T, plasma HDL and apoprotein-AI decreased, but these decreases did not achieve statistical significance. Only a small decrease in HDL2 cholesterol was seen in these men. There were no hormonal or lipid changes in the placebo group. We conclude that in men, physiological levels of E2 are important in maintaining plasma levels of HDL cholesterol, especially the HDL2 fraction. These observations suggest that estrogen, in the amount normally produced in men, may offer some degree of protection against cardiovascular disease in males, as they do in women.

Chylomicrons or their remnants penetrate rabbit thoracic aorta as efficiently as do smaller macromolecules, including low-density lipoprotein, high-density lipoprotein, and albumin

Abstract: BACKGROUND: The aortic accumulation of chylomicrons, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and albumin were compared in normal New Zealand White rabbits. METHODS: Lipoproteins and albumin were labelled with radioiodinated tyramine cellobiose (TC) to avoid potential oxidative modification of lipoproteins and as a marker of intracellular degradation. In preliminary experiments it was established that TC labelling did not alter the kinetic properties of lipoproteins in vivo. Importantly, radiolabelled apolipoproteins did not transfer significantly between plasma lipoproteins. Therefore, aortic radioactivity following infusion of TC-radiolabelled lipoproteins was considered to be indicative of lipoprotein accumulation. RESULTS: In conscious rabbits, net aortic accumulation of chylomicrons or their remnants was similar to those of LDL, HDL and albumin up to 2 h after infusion, despite rapid clearance from plasma. When accumulation was calculated on the basis of mean arterial exposure to allow for the differences in plasma clearance, the accumulation of aortic chylomicrons/remnants was substantially greater than that of LDL, HDL or albumin. Qualitatively similar results were obtained in rabbits that were functionally eviscerated to slow clearance of chylomicron remnants. Chylomicrons/remnants did not appear to efflux from aortic tissue as rapidly as did LDL or other plasma lipoproteins. Autoradiographic analysis showed that the primary site of lipoprotein accumulation was within medial smooth muscle cells. CONCLUSION: Our data demonstrate that chylomicrons/remnants accumulate in arterial blood vessels more rapidly than does LDL, suggesting that dietary lipoproteins may be directly involved in the pathogenesis of atherosclerosis.

Transport of alpha-tocopherol in Atlantic salmon (Salmo salar) during vitellogenesis

Abstract: The transport of α-tocopherol was studied during vitellogenesis in Atlantic salmon that were fed diets with two levels of α-tocopherol. α-Tocopherol levels were measured in the flesh, liver, ovary and serum, and in the serum the α-tocopherol levels in the very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and very high density lipoprotein (VHDL or vitellogenin) were also measured.Atlantic salmon store α-tocopherol mainly in their flesh because the muscle mass comprises 50% or more of live weight. During vitellogenesis the α-tocopherol content declined to about 10% of the level prior to maturation. The relative range of level of α-tocopherol in the lipoproteins was: HDL> LDL> VLDL> VHDL, irrespective of dietary levels of α-tocopherol.From the recent knowledge on lipid transport during vitellogenesis and the present data, we hypothesize that α-tocopherol is transported from peripheral tissues to liver by HDL and further transported from liver to ovary by LDL. Vitellogenin appears to play a minor role in the transportation of vitamin E to the ovary.

Biological variability of cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B.

Abstract: Biological variability is a major contributor to the inaccuracy of cardiovascular risk assessments based on measurement of lipids, lipoproteins, or apolipoproteins. We obtained estimates of biological variation (CVb) for 20 healthy adults and calculated the percentiles of CVb as an expression of the variability of CVb among individuals for cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] by four biweekly measurements of these analytes. The CVb for the group was approximately 6-7% for cholesterol, HDL cholesterol, apo A-I, and apo B; approximately 9% for LDL cholesterol; and 28% for triglyceride. However, for each analyte, there was a considerable variation of CVb among individuals. For all analytes except Lp(a), there was no relation between the individual's CVb and the analyte concentration. Lp(a) was inversely related to CVb, and there was a very wide variation in the CVb for Lp(a) among the participants, ranging from 1% to 51%. The number of independent analyses to perform to accurately assess an individual's risk for coronary artery disease should be determined on the basis of the individual CVb for a given analyte rather than the average CVb.

Physical Activity and Lipoprotein Lipid Disorders

Abstract: Working muscle plays a central role in the control of lipid metabolism. Increased physical activity induces a number of positive changes in the metabolism of lipoproteins: serum triglycerides are lowered by the increased lipolytic activity and the production of native high density lipoprotein (HDL) particles is increased. The increased lecithin: cholesterol acyltransferase activity leads to an increased production of HDL2, which in addition is catabolised more slowly due to a decreased activity of hepatic lipase. The 3 effects explain the increased HDL levels of endurance trained individuals. These effects have been demonstrated in cross-sectional as well as longitudinal studies by different groups, and can be induced by training, independent of changes in body weight. The influence of endurance activity on the quality and quantity of low density lipoprotein (LDL) particles is a further reason for the antiatherogenic potential of increased physical activity. It has been shown by several groups that small dense LDL particles represent a particular risk factor for atherosclerosis. Recent studies presented strong evidence that LDL level and composition can be influenced favourably by physical activity. In addition to the direct influence of physical activity on lipids and lipoproteins, physical exercise may improve the disturbances of haemorheological factors, particularly those associated with hypertriglyceridaemia.

Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol.

Abstract: BACKGROUND In animal models of atherosclerosis, augmentation of circulating high-density lipoprotein (HDL) cholesterol exerts a protective effect against development of fatty streaks and promotes plaque regression. METHODS AND RESULTS To investigate the potential of gene transfer to increase HDL cholesterol, a fusion gene encoding human apolipoprotein A-I (apo A-I) under the control of the human cytomegalovirus (CMV) immediate-early promoter was packaged into a recombinant adenovirus (AdCMV apo A-I). BALB/c mice infected with AdCMV apo A-I by intravenous injection accumulate immunoreactive apo A-I in serum; levels 5 days after infection averaged 168 mg/dL. A 35% increase in HDL cholesterol and a 47% increase in total cholesterol were observed in mice infected with AdCMV apo A-I compared with control viruses. Analysis of size-fractionated lipoproteins revealed that human apo A-I is incorporated into murine HDL particles. Expression of human apo A-I declined to CONCLUSIONS We conclude that adenovirus-mediated transfer of a gene encoding apo A-I produces transient elevations of circulating HDL cholesterol of a magnitude correlated with important physiological effects. These observations suggest the potential for gene-based therapeutic strategies to reduce cardiovascular risk.