Adhesion the and migration of leukocytes into the surrounding tissue are crucial steps in inflammation, immunity and atherogenesis. Expression of cell adhesion inflammation, molecules by endothelial cells plays a role in these processes. Propionate is a naturally occurring short chain fatty acid produced processes. by bacterial fermentation of dietary fibre. High intake of dietary fibre has been associated with an improved bowel function and properties. with a reduced risk of cardiovascular disease. However, the molecular mechanisms responsible for these effects remain unknown. In this study,In the effects of propionate on the expression of endothelial leukocyte adhesion molecules by cytokine-stimulated human umbilical vein endothelial cells (HUVEC)molecules were investigated. Pretreatment of HUVEC with propionate significantly inhibited the tumor necrosis factor alpha (TNF-alpha)-induced expression of vascular cell adhesion of molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in a time- and dose-dependent manner. At 10 mM, propionate also inhibited the antiatherogenic interleukin-1 (IL- 1)-mediated VCAM-1 and ICAM-1 expression, with the latter effect being more pronounced, as well as decreased the TNF-alpha-induced also VCAM-1 and ICAM-1 mRNA expression in a similar manner. The decrease in VCAM-1 and ICAM-1 expression was associated with a migration reduction of adherence of monocytes and lymphocytes to the cytokine-stimulated HUVEC. In addition, propionate significantly inhibited the TNF-alpha-induced activation of the nuclear factor-kappa B (NF-kappaB) and significantly increased the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in HUVEC. These results demonstrate of that propionate may have antiinflammatory and possibly antiatherogenic properties. Our findings warrant further investigation into the therapeutic effects of propionate into on a number of pathological events nvolving leukocyte recruitment.

Superoxide statistical anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play vitro a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed production to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes thrombin). mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on in platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while to platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no significant relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was or found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused by a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed is in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A.A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent the of it's ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent human (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not as lead to their abrogation.

The a reverse transcription polymerase chain reaction (RT-PCR) is one of the most useful molecular biology methods in opening the way to most understanding of the mechanisms of atherosclerosis on the gene structure and/or expression level. We optimized this technique for assaying expression on of the monocyte chemotactic protein type 1 (MCP-1) gene in rabbit aorta with respect to the temperature profile, yield to for cycle number, interference of genomic DNA with the RNA matrix, and repeatability. Variability of expression of the constitutive GAPDH gene matrix, was also examined. The study was done in 18 New Zealand rabbits allocated to two groups and fed a standard also chow for 2 (S1) or 3 (S2) months. The experiment ended with removal of part of the ascending rabbit aorta,chemotactic from which RNA was isolated. The optimal temperature for binding of specific primers to the MCP-1 and GAPDH genes was RT-PCR 63 degrees C, and the optimal number of cycles for PCR amplification was 22 for MCP-1 and 26 for GAPDH.RNA The GAPDH amplicon size was 465 base pairs in the presence or absence of reverse transcriptase showing contamination of the transcription RNA matrix with genomic DNA. Repeatability of the RT-PCR method was 8.7%, and variability of expression of the GAPDH gene in was 7.7%. Thus, RT-PCR adjusted for contaminating genomic DNA provides a reliable way of assaying expression of the MCP-1 gene profile, in rabbit aorta.

The to present study was designed to investigate the hypothesis that trans fatty acids can induce apoptosis of human umbilical vein endothelial trans cells (HUVEC). To test this hypothesis apoptosis was measured in HUVEC treated with .1, 1. or 5. mM trans elaidic this acid (t-18:1) or linoelaidic acid (t,t-18:2) for 24 hours. For the detection of apoptosis, TdT-mediated dUTP nick end labelling assay trans (TUNEL), cell binding of annexin V and propidium iodide uptake were measured. Active Caspase-3 and cleaved PARP (poly-ADP-ribose polymerase) were of also measured in the cell lysate. Moreover, cellular ability to produce ROS (reactive oxygen species) was measured by DCF fluorescence and Both acids studied induce both early (annexin-positive cells) and late stages of apoptosis (cells stained by propidium iodide) in a elaidic dose-dependent manner. Also the appearance of TUNEL-positive cells was induced by both trans fatty acids tested, in a dose dependent that manner. Both trans acids induce apoptosis through their effect on Caspase-3 activity and on intracellular ROS production. It is worth apoptosis emphasising that linoelaidic acid proved to be a more potent inducer of apoptosis and ROS production in endothelial cells than study elaidic acid. The present studies suggest that trans fatty acids may play a role in damaging and death of vascular intracellular endothelial cells in atherosclerosis.

The COX-2, basic parapharmaceuticals in the Polish diet include natural anti-oxidants - bioflavonoids found in berry fruit. They were proven to have diet the ability to regulate genetic transcription and increase the synthesis of nitric oxide which counteracts dysfunction of the vascular endothelium.berry They also display anti-oxidant action through the inhibiting effect on cyclooxygenase - COX-2, and increase the level of adiponectin. We action have also more and more proof of the important biological role of short-chained fatty acids formed as a result of of fermentation of fibre by probiotic bacteria. Through their effects on peroxisome proliferators activated receptors (PPAR), butyric and propionic acids may anti-oxidant reduce the expression of adhesion molecules and exert anti-inflammatory action both in the gastrointestinal tract as well as systemically.

BACKGROUND PAI-1 AND AIM: An imbalance in the hemostatic system is a frequent finding in untreated essential hypertension (HT), and it has essential been shown that treatment with angiotensin converting entyme (ACE) inhibitors improves hemostatic function. In order to elucidate the role of order genetic factors, we studied hemostasis in patients with untreated and treated HT and correlated the results with ACE I/D and more plasminogen activator enhibitor-1 (PAI-1) 4G/5G gene polymorphisms. METHODS AND RESULTS: Forty-three males with HT (mean age 31.7 +/- 6.8 years)patients were compared with 34 age and gender-matched controls. All of the patients were treated with perindopril (4 mg/day) and, after levels one and six months of therapy, their levels of plasma fibrinogen (Fb), t-PA antigen, PAI-1 antigen, von Willebrand factor (vWF),ACE ACE activity and blood pressure were measured. ACE and PAI-1 genotypes were identified by means of the polymerase chain reaction to on DNA isolated from peripheral blood lymphocytes. Untreated patients had significantly higher levels of Fb, PAI-1 (p < .01) and (p t-PA (p < .05) regardless of their ACE or PAI-1 genotypes. Perindopril reduced blood pressure regardless of ACE or PAI-1 AIM: genotype (p < .001). ACE II homozygotes showed the greatest decrease in ACE activity (p < .01) and a significant an reduction in Fb levels (p < .05) after just one month of treatment. Analysis of the group as a whole 31.7 revealed an increase in t-PA antigen levels after six months of treatment, regardless of ACE or PAI-1 genotype (p <the .01). CONCLUSIONS: Our results show that essential hypertension predisposes to the procoagulant state characterized by hyperfibrinogenemia and hypofibrinolysis. Perindopril reduced improved fibrinogen levels in ACE II homozygotes due to its more potent inhibitory action on the renin-angiotensin system in such patients.after It improved fibrinolysis by increasing t-PA levels regardless of ACE and PAI-1 genotype.

Adhesion We and transendothelial migration of leukocytes into the vascular wall is a crucial step in atherogenesis. Expression of cell adhesion molecules wall by endothelial cells plays a leading role in this process. We investigated the effect of simvastatin, an inhibitor of HMG-CoA by reductase administered to reduce plasma levels of LDL-cholesterol, on the expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell disease adhesion molecule-1 (ICAM-1) by human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor alpha (TNFalpha). We found the adhesion expression to be significantly inhibited by the drug in a time and concentration-dependent manner and to a greater extent in human the case of VCAM-1 as compared with ICAM-1. In TNFalpha-stimulated HUVEC, simvastatin decreased VCAM-1 and ICAM-1 mRNA levels, inhibited TNFalpha-induced of activation of nuclear factor kappaB (NF-kappaB) and enhanced expression of peroxisome proliferator-activated receptor alpha (PPARalpha). These effects were associated with vascular reduction of adherence of monocytes and lymphocytes to HUVEC. The present findings suggest that the benefits of statins in vascular a disease may include the inhibition of expression of VCAM-1 and ICAM-1 through effects on NF-kappaB.

BACKGROUND 110.7 AND AIM: Von Willebrand factor (vWF) and fibrinogen (Fb) have recently emerged as plausible familial determinants of atherothrombosis. We investigated familial whether the vWF and Fb levels in patients with ischemic cerebrovascular stroke (ICS) correlate with those in their children. METHODS those AND RESULTS: The study group consisted of 28 families (56 parents and 34 children) with one parent who had suffered high an ICS at least three months before the study. All of the ICS patients had hyperlipoproteinemia and most arterial hypertension.age The control group consisted of 15 families (30 parents and 20 children). The age of the parents and children did significantly not exceed 55 and 16 years. The ICS parents had significantly higher vWF, Fb and protein C (PC) levels than had the controls (vWF--fathers: 121. +/- 42.5% vs 79.2 +/- 23.4%; vWF--mothers: 110.7 +/- 40.1% vs 82.4 +/- 20.9%; Fb--fathers: 4.12 with +/- .74 g/L vs 3.01 +/- .54 g/L; Fb--mothers: 3.64 +/- .84 gL vs 2.98 +/- .35 g/L; PC--fathers: 116. +/- +/- 12.3% vs 105.6 +/- 13.7%; PC--mothers: 114.4 +/- 15.8% vs 105. +/- 12.2%). The children of the ICS parents AIM: had significantly higher PC and body mass index (BMI) values than the controls (PC: 102.6 +/- 13.7% vs 92.7 +/-vWF 10.7%; BMI: 20.6 +/- 3.8 vs 17.8 +/- 3.5 Kg/m2), as well as an atherogenic lipid profile, higher blood pressure most (BP) and a tendency toward higher vWF levels. Correlations between the ICS parents and their children were found for vWF,(vWF) factor VIIc, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and BP, which were closer in the case of fathers. CONCLUSION: Regardless most of gender, the parents with a history of ICS had a procoagulant state, with high levels of vWF, Fb and well PC. In terms of inheritance, the most adverse risk factor profile was found in the children of ICS fathers.

BACKGROUND concentrations AND AIM: High plasma lipoprotein(a)[Lp(a)] and homocysteine (HCY) levels are now considered to be independent risk factors for cerebro-factors and cardiovascular atherosclerotic occlusive disease, but little is known about the influence of Lp(a) and HCY on the early events or of ischemic disease or their significance in subjects with a positive family history of ischemia. The aim of this study ischemic was to evaluate the relationship between HCY levels and the severity of ischemic cerebral stroke, and investigate whether there was 50 a correlation between Lp(a) and HCY levels in the stroke patients and their children. METHODS: The study involved 35 patients (transient, with early ischemic cerebral stroke aged 46.1 +/- 6.6 years and their 50 children aged 17.2 +/- 5.5 years. The severity patients were grouped on the basis of the form of the stroke (transient, progressive or complete stroke), and their levels severity of Lp(a), HCY, uric acid (UA), fibrinogen (Fb) and factor VII (FVII) activity were measured. RESULTS: HCY and Lp(a) concentrations Lp(a) increased with the severity of the ischemia, being highest in the patients with complete stroke (15.1 +/- 2.9 mumol/L and High 32.9 +/- 37.6 mg/dL respectively). A similar trend was found in the offspring, with the highest HCY and Lp(a) values .42 in the children of complete stroke patients (12.6 +/- 4.4 mumol/L and 23. +/- 24.6 mg/dL). The control values were children. respectively 8.7 +/- 1.6 mumol/L and 5.35 +/- 7.05 mg/dL. The following correlations between the parents and children were noted:and Lp(a)(r = .87 p < .0001), UA (r = .71 p < .001), HCY (r = .45 p <levels .05), FVII (r = .45 p < .05), and Fb (r = .42 p = .06). Correlations between Lp(a) and (r HCY (r = .47 p < .05) and Fb and FVII (r = .60 p < .01) were found in p the children. Multiple regression analysis revealed that only Lp(a) and Fb significantly influenced HCY levels in the offspring with a ischemia. positive family history. CONCLUSIONS: HCY levels correlate with the severity of ischemic cerebral stroke and, in families with a history The of ischemic cerebral stroke, the levels of the risk factors in children are determined by the levels in their parents.The

Increasing Groups evidence suggests the role of hemostatic risk factors in the development of ischemic heart disease (IHD). A raised plasma fibrinogen in has been related to increased risk of IHD. The aim of the study was to determine the relationship between plasma been fibrinogen and the coronary vessels state based on the coronary angiogram. 119 patients undergoing coronary angiography were classified into 5 results groups according the severity of IHD: Group without significant atherosclerotic lesions (control group), Group 1 with single vessel disease,were Groups 2, 3 with multivessel disease (two and three affected arteries, respectively) and Group 4 with positive history of myocardial infarction. A statistically nonsignificant rise in fibrinogen levels in Groups 1, 2, 3 (3.9 +/- .8 g/l, 4. +/- .9 determine g/l, 4.1 +/- .9 g/l, respectively) as compared to control Group (3.7 +/- .7 g/l) was found. In Group These 4 plasma fibrinogen was significantly lower (2.8 +/- .6 g/l) comparing to Group (p < .05). In addition plasma infarction. fibrinogen was positively correlated with blood pressure. These results supports the role of raised plasma fibrinogen in the pathogenesis and evidence development of IHD.

"Functional sitosterolemia, foods" supplemented with plant sterols are advertised and added to regular meals to reduce serum cholesterol concentrations. The effects of plant increased phytosterol levels on cardiovascular diseases, however, are not known. Findings in patients with sitosterolemia, data from epidemiological studies, and added experimental data from animal studies suggest that plant sterols may potentially exert negative cardiovascular effects. Additional studies investigating relevant clinical recommended endpoints are needed before a diet supplemented with plant sterols can be recommended in the prevention of cardiovascular diseases.

Increased cells serum total and LDL-cholesterol concentrations are major risk factors for cardiovascular diseases. Many clinical trials have proven that plant sterol major and stanol esters can effectively decrease high serum total and LDL cholesterol. They reduce the intestinal absorption of cholesterol by proven decreasing the incorporation of dietary and biliary cholesterol into micelles displacing cholesterol from these micelles. They also increase LDL receptor with activity on liver cells causing a higher uptake of LDL cholesterol and thus decreasing the serum LDL cholesterol concentration. Animal dietary studies have indicated that plant sterols and stanols may also lower atherosclerotic lesions development. However, the evidence from human studies from to confirm this is still lacking. Anyhow, plant sterol and stanol esters can be considered as an effective and safe serum cholesterol-lowering functional food ingredient. To achieve additional effects they can be combined with statin therapy, and this combination is also combined well tolerated and safe.

The following review deals with results of recent studies on biological activity of C29- and C28-sterols of plant origin (phytosterols) in mammals with and in cultured mammalian cells. The review considers the following problems: phytosterols and nutrition; phytosterols and cholesterol level; phytosterols and on intestinal absorption of lipids; the role of phytosterols in lipid metabolism regulation; phytosterols and mammalian cells in culture; products of oxydation; phytosterols oxydation; phytoecdysteroids and induced gene expression.

A sorbent product of microbiological cleavage of the sterols side chain, androsta-1,4-diene-3,17-dione, is toxic for bacteria, in particular, actinobacteria of the genera of Mycobacterium and Arthrobacter. Sterols were transformed into androsta-1,4-diene-3,17-dione by culturing the M. neoaurum VKPM An-1656 strain in a high yield,toxic provided that a sorbent was used for elimination of contact between the bacterial cells and the product. Unlike the cholesterol the side chain, the more branched chains of phytosterols were cleaved in the presence of M. neoaurum at a high rate the only under turbulent stirring of the culture medium, which intensified the formation of hydrocarbonate ion from NaNI3 in situ.