Impact of obesity and nitric oxide synthase gene G894T polymorphism on essential hypertension.

Hypertension is a multifactorial disease caused by environmental, metabolic and genetic factors, but little is currently known on the complex interplay between these factors and blood pressure. The aim of the present study was to assess the potential impact of obesity, and angiotensin-converting enzyme (ACE) I/D polymorphism and endothelial nitric oxide synthase gene (NOS3) 4a/4b, G894T and -T786C variants on the essential hypertension. The study group consisted of 1,027 Caucasian adults of Polish nationality (45.5 ± 13.6 years old), of which 401 met the criteria for hypertension. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides were determined by standard procedures. The ACE I/D polymorphism and three polymorphisms in NOS3 gene (4a/4b, G894T, -T786C) were detected by the PCR method. Multivariable logistic regression demonstrated that age above 45 years, diabetes, dyslipidemia, smoking and male sex are important risk factors for hypertension and no significant influence of variants in ACE and NOS3 genes on this risk was recognized. Obese subjects had a 3.27-times higher risk (OR = 3.27, 95% CI: 2.37 - 4.52) of hypertension than non-obese, and in obese the NOS3 894T allele was associated with 1.37 fold higher risk of hypertension (P = 0.031). The distribution of NOS3 G894T genotypes supported the co-dominant (OR = 1.35, P = 0.034, Pfit = 0.435) or recessive (OR = 2.00, P = 0.046, Pfit = 0.286), but not dominant model of inheritance (P = 0.100). The study indicates that in obese NOS3 G894T polymorphism may enhance hypertension risk. However, in the presence of such strong risk factors as age, diabetes and smoking, the impact of this genetic variant seems to be attenuated. Further studies are needed to reveal the usefulness of G894T polymorphism in hypertension risk assessment in obese.

Conformation and elasticity of a charged polymer chain bridging two nanoparticles.

A complex composed of a charged flexible polymer chain irreversibly attached with its ends to surfaces of two nanoparticles was investigated using the Metropolis Monte Carlo method on a simple cubic lattice. The simulations were performed in the presence of explicit ions. The bridging chain and the nanoparticles bearing the same and the opposite sign charges were considered. Changes in the free energy of the complex upon its stretching or compression, together with the magnitude of the elastic force, were examined. The relative roles of energetic and entropic effects in determining the properties of the complex were identified. Also, the adsorption of charged monomers on the opposite-sign charged nanoparticles and its influence on the examined quantities was studied. Moreover, a simple semi-analytical approach to the thermodynamics of the polymer bridge was derived.

Spontaneous processes and stable structures in some three-phase cellular fluids.

Cellular fluids are systems consisting of a collection of fluid cells surrounded by thin liquid films. In this study, systems composed of two different kinds of cells (i.e., filled with fluids A and B) immersed in a third fluid phase (a liquid C) have been examined. The object of the study is a collection of polyhedra of fluid B separated by a thin film of liquid C (a host B/C network), modified by the insertion of small droplets/bubbles of fluid A. Interfacial tensions acting along the A-C and B-C interfaces are assumed to be the only driving forces determining the structure of the resulting mixed system. Different configurations of mixed A/B/C systems, formed by the insertion of A singlets or doublets into the nodes, edges, films and interior parts of cells of the B/C network have been analyzed in terms of the interfacial energy of the system. The possibility of spontaneous migration of cells A through the B/C network and the possible final cell arrangements have been examined.

The interfacial energy of two-dimensional bidisperse cellular fluids.

Abstract. The mixing energy of two biphasic fluid systems (dispersions of two liquids or a liquid and a gas, A and B in a liquid C), confined between two parallel plates, is calculated. Our attention is limited to concentrated and monodisperse systems, i.e. emulsions and foam/emulsions consisting of equal-size (if of the same composition) cells separated by a thin liquid film. It is demonstrated that the multiphase mixtures ordered into regular patterns can be stable in a wide range of interfacial tensions acting along A-C and B-C interfaces and also in a wide range of volume fractions of fluid A. Anisotropic properties of such well-ordered structures are also demonstrated.

LpAI in HDL subfractions: serum levels in men and women with coronary heart disease and changes under hypolipemic therapy.

BACKGROUND: It is generally accepted that different HDL subpopulations may vary in their antiatherogenic potential, and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL particle groups. METHODS: In the present study, LpAI particles concentrations in HDL(2) and HDL(3) subfractions were determined in serum of 54 CHD patients (33 men and 21 women) and 46 control subjects (19 men and 27 women) with similar total cholesterol and HDL-cholesterol levels. RESULTS: In CHD patients, both men and women, as compared to control subjects lower levels of LpAI subpopulations were found, however, the difference was much more predominant for LpAI-HDL(2) than for LpAI-HDL(3). The effect of hypolipidemic treatment on the distribution of LpAI subpopulations between HDL subfractions was investigated in 44 hyperlipidemic patients assigned to fenofibrate therapy and 43 patients assigned to simvastatin therapy. Fenofibrate did not change LpAI level but had an effect on LpAI particle distribution among HDL(2) and HDL(3) increasing LpAI concentration in HDL(2) and slightly decreasing LpAI concentration in HDL(3). Simvastatin led to an increase in LpAI-HDL(3) and did not change significantly LpAI-HDL(2) particle concentration. CONCLUSION: Further studies are needed to evaluate the significance of different HDL subpopulations.

[The atherogenic lipid profile parameters and fibrinogen serum concentration in climacteric women under various routes of hormone replacement therapy administration]. / Ocena stezenia aterogennych czynników lipidowych i fibrynogenu w surowicy kobiet stosujacych rózne formy hormonalnej terapii zastepczej w okresie klimakterium.

OBJECTIVES: Influence of various routes of HTR on atherogenic lipid profile parameters and serum fibrinogen concentration was investigated. DESIGN: In 85 women in four groups receiving HRT transvaginally, transdermally, orally and intramuscularly, the total cholesterol, HDL-cholesterol, triglycerides, apoB, apoA, LpA and fibrinogen serum concentration was assessed before treatment and after six month. RESULTS: Most of tested parameters: total cholesterol, LpAI, apoB, LDL cholesterol, non HDL cholesterol, changed favorably (lowered concentration) in group using HRT orally and intramuscularly. CONCLUSION: Orally and intramuscularly route of administration HRT have better cardioprotective effects.

Apolipoprotein E polymorphism in alagille syndrome and progressive familial intrahepatic cholestasis.

The aim of the study was to assess the apolipoprotein E polymorphism (apoE) in two familial cholestatic diseases-Alagille syndrome (AS) and progressive familial intrahepatic cholestasis (PFIC)-and to estimate its association with gallstone formation, cholesterol levels, and response to UDCA treatment. We investigated 16 children with AS age 8.8 +/- 5.7 years (mean +/- SD) and 18 children with PFIC age 6.3 +/- 4.6 years. The frequency of the epsilon-2 allele in AS and PFIC was higher and the frequency of the epsilon-3 allele was lower than in controls. Gallstones were diagnosed in nine children with PFIC and different apoE phenotypes. No association between phenotype and cholesterol levels or response to UDCA therapy was observed in the patients studied. In conclusion, the allele epsilon-2 is overrepresented in AS and PFIC, similar to primary biliary cirrhosis, although this does not seem to contribute to different cholesterol levels, gallstones, and response to UDCA therapy.

Comparative analysis of plasma lipoprotein components assessed by ultracentrifugation in primary biliary cirrhosis and chronic hepatitis.

UNLABELLED: The evaluation of lipid and lipoprotein profiles in liver diseases has important cognitive aspects and provides practical information contributing to the diagnosis of liver pathology. There are few studies of this problem using the ultracentrifugation method. AIM OF THE STUDY: A comparison of lipid profile (obtained by plasma ultracentrifugation) in patients with primary biliary cirrhosis (PBC) and chronic hepatitis (CH). MATERIAL AND METHODS: 103 percutaneous liver biopsies were routinely performed from 1994 to 1997. Blood samples were taken from all the patients at the time of biopsy for further evaluation of lipid profile. 15 patients with PBC and 15 patients with CH (of HBV or/and HCV etiology) were studied. RESULTS: In patients with CH mean total, esterified and free cholesterol levels (166 mg%, 117.6 mg% and 48.1 mg%, respectively) were significantly lower (p < 0.002; p < 0.004; p < 0.006, respectively) than in patients with PBC (237.5 mg%, 165.7 mg% and 71.8 mg%, respectively). The phospholipid concentration in sera of patients with PBC were significantly higher (271.1 mg%, p < 0.0004) than in patients with CH (187.6 mg%), whereas apolipoprotein B and apoAII were significantly lower. Total, esterified and free cholesterol levels in LDL fraction were significantly higher in patients with PBC (175.3 mg%, p < 0.007; 117.9 mg%, p < 0.02; 57.6 mg%, p < 0.01, respectively) than in patients with CH (113.7 mg%, 78.7 mg% and 35 mg%, respectively). The concentration of phospholipids in LDL fraction in patients with PBC was significantly higher (166.8 mg%; p < 0.003) in comparison with patients with CH (96.3 mg%). The differences in other lipoprotein fractions (VLDL and HDL) were not statistically significant. CONCLUSIONS: High levels of total, free and esterified cholesterol as well as phospholipids, apolipoprotein B and AII were observed by us in patients with PBC in comparison with patients suffering from CH. The increase of cholesterol (total, esterified and free) and the phospholipid concentration in serum, are a manifestation of their higher concentration in LDL fraction.

Lipids in serum of patients with malignant ovarian neoplasms.

OBJECTIVE: In numerous papers, different associations of serum lipids and lipoproteins with neoplastic diseases were found. The aim of our work was to find out associations between levels of 11 serum lipids, lipoproteins and ovarian cancer. METHODS: 25 healthy women and 25 patients with ovarian cancer underwent examinations. Uni- and multivariate analysis of variance and discrimination analysis were used to analyze our results. RESULTS: The analysis demonstrates that ovarian carcinoma is associated with a significant reduction of total cholesterol and its esters in serum and in high density lipoprotein fractions compared to controls. CONCLUSION: It could be shown that using multivariate analysis of variance it is possible to find the optimal set of serum lipid parameters, containing serum esterified cholesterol, serum total cholesterol and high density lipoproteins esterified cholesterol, to differentiate healthy persons from patients affected by ovarian cancer.

[Risk factors for coronary heart disease in 1002 patients with hyperlipidemia]. / Czynniki ryzyka choroby niedokrwiennej serca u 1002 pacjentów z hiperlipidemia.

The aim of this study was to estimate the coexistence of risk factors for coronary heart disease (CHD) in hyperlipidemic patients. Studies were performed in 1002 (601 women, 401 men) subjects who referred to our outpatient clinic among 12 months. Hypercholesterolemia was the predominant lipid disorder found in 66% of patients, mixed hyperlipidemia in 31.8%, and hypertriglyceridemia only in 2.2%. Overweight and obesity remain a major health burden among our patients: BMI > or = 25 was observed in 66%. Hypertension was recognized in 37.5% of subjects, and diabetes mellitus in 11.2%, 17% were long-term smokers. Familial aggregation of hyperlipidemia was observed in 15.7% of subjects, and more than 44% had a positive family history of cardiovascular disease. Low HDL cholesterol levels (< 35 mg/dl) were seen frequently in men (24.7%) and rare in women (7%). Lp(a) excess (> or = 30 mg/dl) was observed in 12% of patients. Myocardial infarction (MI) had already 11.7% subjects (7% women, 18.7% men). In these patients CHD risk factors were observed more frequently. The higher apo B and Lp(a) levels and lower HDL cholesterol levels were recognized in the patients who suffered from MI. More than 83% of our hyperlipidemic patients had coexistence CHD risk factors. The multiple coexisting risk factors cause the high risk for CHD and they require intensive correction.

[Influence of fish oil on serum lipoprotein level in endogenous hypertriglyceridemia]. / Wplyw oleju rybnego na poziom lipoprotein surowicy w hipertriglicerydemii endogennej.

The influence of fish oil on the level and composition of lipoprotein fractions in hypertriglyceridemic men was evaluated. The observation was performed in 2 groups of patients, 10 cases each (a cross-over study). In the group I subjects received fish oil first, in the dose of 12 grams daily (3.6 g of EPA and DHA) for 3 weeks, and then, for the next 3 weeks, olive oil in the same dose. Patients from the group II received the same oil but in the inverse order. Results after olive oil were a control for fish oil. Marked decreases in the serum and VLDL triglycerides and also VLDL-cholesterol level after fish oil was shown. Increases in LDL and HDL cholesterol were observed. In 9 patients fish oil was given for 6 weeks. No differences in the serum lipid levels after this period of time in comparison with results after 3 weeks were observed.

[Comparative study of the influence of fish oil and gemfibrozil on levels of serum lipoprotein in endogenous hypertriglyceridemia]. / Badanie porównawcze wplywu oleju rybnego i gemfibrozilu na poziom lipoprotein surowicy w hipertriglicerydemii endogennej.

Hypolipemic action of fish oil and gemfibrozil was compared. The study was performed in 12 men with endogenous hypertriglyceridemia. Subjects received fish oil 12 grams daily (3.6 g of eicosapentaenoic and docosahexaenoic fatty acids) for 3 weeks, and then, after an interval of at least 6 weeks, gemfibrozil in the dose of 900 mg daily. Results after gemfibrozil were compared with those after fish oil. Fish oil was shown to be less effective than gemfibrozil in decreasing concentrations of serum triglycerides and triglycerides and cholesterol in VLDL. However, the difference did not reach the level of statistical significance. The agents differed significantly in their influence on the LDL fraction. Fish oil slightly increased and gemfibrozil significantly decreased LDL-chol level. LDL-apoB increased after fish oil, but did not change after gemfibrozil. It may be concluded that fish oils, although effective in decreasing concentrations of serum triglycerides and lipid components of the VLDL fraction, are not alternative for gemfibrozil in monotherapy of endogenous hypertriglyceridemia.

High density lipoprotein deficiency with xanthomas. A defect in reverse cholesterol transport caused by a point mutation in the apolipoprotein A-I gene.

A 7-yr-old girl with high density lipoprotein (HDL) deficiency and xanthomas has been identified in a Turkish kindred with repetitive consanguinity. She has severely reduced HDL-cholesterol and no apolipoprotein (apo) A-I. ApoA-II is reduced, whereas apoA-IV and apoC-III are normal. ApoB and low density lipoprotein (LDL)-cholesterol are increased. This is reflected in hypercholesterolemia. VLDL and IDL particles are low, and serum triglycerides are normal. The genetic defect could be identified as a base insertion into the third exon of the apoA-I gene. This leads to a nonsense peptide sequence beginning at amino acid 5 of the mature plasma protein and early termination of translation. The patient is homozygous for this mutation. Pedigree analysis indicated an autosomal dominant inheritance with no evidence of another genetic defect of lipoprotein metabolism in the kindred. In HDL deficiency, HDL binding to leukocytes was increased compared to normal. In the postprandial state, binding of labeled HDL3 to leukocytes is unchanged. This is in contrast to results with postprandially isolated leukocytes from controls or Tangier patients, which have a reduced binding capacity for HDL3. These results indicate that postprandial HDL precursors may compete the binding of labeled HDL3. The metabolic consequences of HDL deficiency were analyzed. There is only a small number of HDL-like particles containing apoA-II, apoA-IV, apoE, and lecithin/cholesteryl acyl transferase. The C-apolipoproteins were normal in the proband. Due to the lack of HDL they can only associate with apoB-containing particles, where they may interfere with cellular uptake. Thus, pure apoA-I deficiency leads to a complex metabolic derangement.

[Effect of combined treatment with lovastatin and colestipol on serum lipids and lipoproteins]. / Wplyw skojarzonego leczenia lovastatinem i kolestipolem na lipidy i lipoproteiny surowicy.

In 20 men with hypercholesterolaemia or mixed hyperlipaemia the effect was evaluated of treatment with Lovastatin and Colestipol on lipoproteins. Administration of the drugs in combination or alone decreased significantly the concentrations of total cholesterol (TC), LDL cholesterol (LDL-chol), and apolipoprotein B (apo B). The combination of Lovastatin in dose of 40 mg with Colestipol in dose of 10 g decreased more favourably the concentrations of TC (34.7%), LDL-chol (44.3%), and apo B (22.4%) than administration of each of the drugs alone in higher doses i.e. Lovastatin 80 mg (TC--26.8%, LDL-chol--31.8%, apo B--16.9%) or Colestipol 20 g (TC -20.0%, LDL-chol-26.3%, apo B-10.8%). The treatment with Lovastatin and Colestipol failed to change significantly the concentrations of triglycerides, HDL cholesterol and AI and AII apolipoproteins. The combined therapy was better tolerated than monotherapy.

[Effect of CRP preparation on serum lipids in patients with hyperlipidemia]. / Wplyw preparatu CRP na lipidy surowicy u pacjentów z hiperlipidemia.

In a group of 18 patients with essential hyperlipidaemia the influence was studied of multivitamin CRP preparation given for 12 weeks, on lipid peroxides, cholesterol and triglycerides in the serum. The level of lipid peroxides was decreased significantly. This effect was associated with the increase of the serum level of vitamin E. A decrease was also found of the levels of total cholesterol and LDL-cholesterol.

Macrophage interaction of HDL subclasses separated by free flow isotachophoresis.

Preparative isotachophoresis (ITP) was used for the fractionation of fasting and postprandial high density lipoproteins (HDL) according to their net charge in the absence of molecular sieve effects. Three major HDL subpopulations with fast, intermediate, and slow mobility have been recognized. Particle size analysis by gradient gel electrophoresis has shown that in the fast-migrating subpopulation particles dominate with a size of HDL3a and HDL2b. The subpopulation with intermediate mobility contains particles with a size between HDL2a and HDL3b, while in the slow migrating subpopulation particles dominate with a size of HDL2b, HDL3a, and HDL3c. The fast-migrating subpopulation is rich in apoA-I and phosphatidylcholine. The particles of this fraction bind at 4 degrees C to HDL receptors on macrophages with high affinity (KD = 7.71 micrograms/ml; Bmax = 245.6 ng). The subpopulations with intermediate mobility is rich in apoA-II, apoE, C apolipoproteins, cholesteryl esters, and sphingomyelin. Its affinity to HDL receptors (KD = 17.7 micrograms/ml; Bmax = 198.4 ng) is lower than that of the HDL particles in the fast-migrating subfraction. The slow-migrating subpopulation consists of particles rich in apoA-IV and is associated with a high LCAT activity. This fraction expresses the highest nonspecific binding to mouse peritoneal macrophages compared to the other HDL fractions and contains only a small amount of particles that interact with HDL receptors by high affinity binding (KD = 7.3 micrograms/ml; Bmax = 95.9 ng). In 37 degrees C binding experiments the fast-migrating subfraction reveals the highest total cell-associated activity. 72% of which is trypsin-resistant. The other subfractions express a lower total cell-associated activity and 45% of the activity of the intermediate- and 43% of the activity of the slow-migrating fraction is trypsin-sensitive. When the HDL fractions are isolated from postprandial sera of the same donor, the fast-migrating particles bind at 4 degrees C with a higher affinity (KD = 4.6 micrograms/ml) while no significant changes are observed in the intermediate- and slow-migrating subpopulations. The slow- and the fast-migrating HDL subpopulations isolated from fasting serum have a high capacity to promote cholesterol removal from macrophages. We hypothesize that the HDL subpopulations rich in apoA-I promote cholesterol removal predominantly via the interaction with HDL receptors, while apoA-IV-rich HDL particles receive their driving force for cholesterol efflux from the concomitant action of LCAT via a predominantly nonspecific interaction of the particles with the cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of phospholipid biosynthesis during cholesterol influx and high density lipoprotein-mediated cholesterol efflux in macrophages.

We have studied the rate of phospholipid synthesis and turnover in mouse peritoneal macrophages in reaction to cholesterol influx and high density lipoprotein (HDL)-mediated cholesterol efflux, using three different radioactive precursors, 32PO4(3-), [3H]choline, and [14C]oleic acid. The cells were loaded with cholesterol for up to 18 h with acetyl-low density lipoprotein (LDL), and phospholipid synthesis was measured at various time intervals and compared with nonloaded macrophages. In the first 2 h of cholesterol loading, a twofold increase in the rate of synthesis for sphingomyelin, phosphatidylcholine, phosphatidylserine-inositol, and phosphatidylethanolamine was observed. After this initial up-regulation, the rate of phospholipid synthesis continuously declined upon further cholesterol loading, while the turnover rate of cellular phospholipids was not affected under the same conditions. The lysosomal inhibitor chloroquine abolished the down-regulation, revealing a strong correlation between phospholipid synthesis and lysosomal enzyme activity which was presumably dependent on the release of cholesterol from the lysosome. The reduction in phospholipid synthesis induced by cholesterol loading is reversible by the addition of HDL3 to the cells. When HDL3 was added to the culture medium, a two- to threefold increase in phosphatidylcholine synthesis and a twofold increase in sphingomyelin formation was observed after 3 h. Ca2+ antagonists of the dihydropyridine type, which down-regulate HDL-receptor activity and promote the formation and cellular release of lamellar bodies derived from the lysosomal compartment (Schmitz, G., et al. 1988. Arteriosclerosis. 8: 46-56, and Robenek, H., and G. Schmitz. 1988. Arteriosclerosis. 8: 57-67), specifically enhance the synthesis of sphingomyelin in cholesterol-loaded macrophages. Inhibitors of acyl-CoA:cholesterol acyltransferase (Octimibate, progesterone) increase both the synthesis of sphingomyelin and phosphatidylcholine, and enhance HDL-receptor activity. The results indicate that cholesterol and phospholipid metabolism are coordinately regulated in macrophages. Moreover, the formation of phosphatidylcholine and sphingomyelin seems to be an important factor for the promotion of HDL-receptor-mediated cellular cholesterol efflux.

Characterization of apolipoprotein B-containing lipoproteins separated by preparative free flow isotachophoresis.

Preparative free flow isotachophoresis (ITP) was used for the fractionation of apoB-containing lipoproteins (d less than 1.063 g/ml) from fasting and postprandial sera derived from normolipidemic individuals. According to their net electric mobility, four major particle groups (I-IV) have been recognized. The fast-migrating particles in group I, which correspond predominantly to very low density lipoproteins (VLDL), are rich in triglycerides, free cholesterol, phosphatidylcholine, and apoE and C apolipoproteins. This group expresses nonspecific binding to fibroblasts but binds to HepG2 cells with high affinity (KD = 3.6 micrograms/ml, Bmax = 37 ng) to a single class of binding sites. The particles migrating in group II, which are related to intermediate density lipoproteins (IDL), are richer in cholesteryl esters and apoB than those in group I. They interact specifically with a single site on fibroblasts (KD = 7.8 micrograms/ml, Bmax = 54 ng) while on HepG2 cells two binding sites, one with a higher (KD = 3.5 micrograms/ml, Bmax = 22 ng) and one with a lower affinity component (KD = 16.9 micrograms/ml, Bmax = 53 ng), are involved. The particles migrating in groups III and IV correspond to low density lipoproteins (LDL). The protein moiety of both fractions consists almost exclusively of apoB. Group III represents cholesteryl ester-rich LDL particles, while the particles in group IV contain smaller amounts of cholesteryl esters. The lipoproteins of both groups are ligands for apoB,E-receptors. However, the particles in group IV interact with fibroblasts with the highest affinity (KD = 2.3 micrograms/ml, Bmax = 58 ng) and with the biphasic HepG2 cell binding sites with the lowest affinity of all analyzed groups (KD1 = 11.2 micrograms/ml, Bmax1 = 58 ng, KD2 = 68 micrograms/ml, Bmax2 = 170 ng). When apoB-containing lipoproteins were isolated from postprandial sera of the same individuals, significant changes in the lipid composition were observed only in particle groups I and II, where the triglyceride and phospholipid content was enhanced. Group I particles from postprandial serum bind to HepG2 cells with a higher affinity (KD = 2.5 micrograms/ml) than group I particles from fasting serum. Postprandial group II particles bind with the same affinity to the biphasic HepG2 cell receptor as fasting group II particles, while the affinities of postprandial group III (KD1 = 4.1 micrograms/ml, KD1 = 47 micrograms/ml) and group IV particles (KD1 = 3.9 micrograms/ml, KD2 = 38 micrograms/ml) to the high affinity binding site of the biphasic receptor are enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)