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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) are associated with aging and the correlation between Alzheimer's disease and atherosclerosis is a subject of the discussion. The aim of this study was to determine whether genetic factors affect cellular defense against cytotoxic beta-amyloid (Abeta) which is considered to be the source of ROS. Low levels of Abeta (1-10 microM) led to a significant suppression of redox potential as measured by MTT assay in bone marrow-derived cell lines. The atherosclerosis-resistant cells (GG2EE) were less affected than the susceptible cells (ANA1) in the time-, dose-, and Abeta species-dependent manner. Cell death in amyloid treated resident susceptible macrophages (C57BL/6J), measured by lactate dehydrogenase release, was induced during prolonged incubation and increased when compared with the resistant macrophages (C3H/HeJ, P = 0.005). SDS-PAGE showed that Abeta persisted intracellularly during this period. The cytotoxicity of oxidized low density lipoproteins (oxLDLs) significantly affected only the susceptible cells which actually lowered this cytotoxicity, thus, implying that the harmful effect of the oxLDLs was diminished when compared to that of Abeta. This fact demonstrates that in vitro the defense by cells of monocyte origin against Abeta may be determined in part genetically whereas the reaction to oxLDLs could be fully underlined by genetic susceptibility.
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PMID:Cellular defense against oxidized low density lipoproteins and fibrillar amyloid beta in murine cells of monocyte origin with possible susceptibility to the oxidative stress induction. 1503 16

We developed myocardial infarction-prone rabbits (WHHLMI rabbits) by selectively breeding coronary atherosclerosis-prone WHHL rabbits. To examine the serum/plasma biochemical parameters of this animal model, we assayed the lipid and glucose levels, and enzyme activities of WHHLMI rabbits from 2 to 26 months of age using solid phase analysis. The results showed a good correlation with those measured with a conventional method. The serum enzyme activities and lipid levels varied with aging despite almost no change in the plasma glucose levels. Gender differences were observed in the total cholesterol, triglyceride, and lactate dehydrogenase activity levels. The data on these serum/plasma biochemical parameters will be useful in studies of myocardial infarction or pharmacological studies using this model.
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PMID:Age-related changes in serum/plasma biochemical parameters of WHHLMI rabbits. 1515 80

Alzheimer's disease (AD) and dementia with vascular component (DVC) are the most prevalent forms of dementia. Both clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folate and vitamin B12 levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: anthropometric values (weight, height); cardiovascular function (ECG, heart rate); blood pressure; lipid metabolism (HDL-CHO, TGs); uric acid metabolism; peripheral calcium homeostasis; liver function (GOT, GPT, GGT); alkaline phosphatase; lactate dehydrogenase; red and white blood cells; regional brain atrophy (left temporal region, inter-hippocampal distance); and left anterior blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Brain perfusion studies show a severe brain hypoperfusion in dementia associated with enlarged age-dependent arterial perfusion times. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30% to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0% to 5%. The relative polymorphic variation in genetic clusters integrated by two, three or four genes associated with AD ranges from 1% to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are determinant for the expression of dementia symptoms which might be accelerated or induced by environmental and/or cerebrovascular factors.
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PMID:Phenotypic profiles and functional genomics in Alzheimer's disease and in dementia with a vascular component. 1526 64

Constitutive genomics are probably determinant for the onset of dementia in conjunction with cerebrovascular and environmental factors. Furthermore, pharmacogenomic studies predict that the therapeutic response in Alzheimer's disease (AD) is genotype-specific, and that the expression of genes involved in the regulation of drug metabolism can influence efficacy and safety issues in pharmacotherapy. AD and dementia with a vascular component (DVC = VD + MXD) are the most prevalent forms of dementia. These clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles, as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folic acid and vitamin B(12) levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: (a) anthropometric values, (b) cardiovascular function, (c) blood pressure, (d) lipid metabolism, (e) uric acid levels, (f) peripheral calcium levels, (g) liver function (GOT, GPT, GGT), (h) alkaline phosphatase, (i) lactate dehydrogenase, (j) red and white blood cells, (k) regional brain atrophy (left temporal region, inter-hippocampal distance) and (l) brain blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30 to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0 to 5%. The relative polymorphic variation in genetic clusters integrated by 2, 3 or 4 genes associated with AD ranges from 1 to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are essential for the expression of dementia symptoms that might be accelerated or induced by environmental and/or cerebrovascular factors.
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PMID:Genomics and phenotypic profiles in dementia: implications for pharmacological treatment. 1534 38

To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atherosclerosis and coronary heart disease. The toxic effects of cholesterol on the liver and the relationship between the intake of a high cholesterol diet and hepatic fibrosis, however, have not been investigated clearly or histopathologically. Male Wistar rats were fed a diet supplemented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacrificed and analyzed via blood biochemistry, traditional microscopy and immunohistochemistry. Following the feeding of this diet, the rates of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total cholesterol in the rats were elevated consistently from week 3 and throughout the remainder of the experiment. From microscopic observation, hepatic necrosis, macrophage infiltration and steatosis increased markedly throughout the experiment. Hepatic fibrosis and myofibroblast proliferation were detected at weeks 9 and 12. Mast cell appearance was proportional to the degree of hepatic damage. These findings suggest that hepatic fibrosis is inducible by a high cholesterol diet and is likely the result of the interaction between several different cell types (i.e., macrophages, myofibroblasts, and mast cells) in an inflammatory milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease.
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PMID:Mild hepatic fibrosis in cholesterol and sodium cholate diet-fed rats. 1580 24

Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer. In the present study, we have synthesized an analog of curcumin and biomonitored its influence over biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats. The effects were compared with that of curcumin, a well-known antioxidant and anti-hyperlipidemic agent. Toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks), and curcumin (80 mg/kg) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Measurements of activities of the biochemical marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase and of plasma lipid profiles were used to monitor the anti-hyperlipidemic effects of curcuminoids. In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed. Administration of curcumin or curcumin analog to nicotine-treated rats significantly reduced the activity of marker enzymes and plasma lipid levels. Thus, our findings suggest that curcumin and its analog exert an anti-hyperlipidemic effect against nicotine-induced lung toxicity and may be a promising agent for treatment of hyperlipidemia and atherosclerosis.
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PMID:Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats. 1611 19

The aim of the present study is to evaluate the effect of eicosapentaenoic acid (EPA), dl-alpha-lipoic acid (LA) and eicosapentaenoate-lipoate (EPA-LA) derivative on the atherogenic disturbances in hypercholesterolemic atherogenic animals. Eight groups of male Wistar rats were employed in this study, wherein four groups were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days, among which, three groups of rats were also treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) commencing from 16th day of the experimental period. The remaining four groups served as control and EPA, LA and EPA-LA derivative treated drug controls. Abnormal increases in the levels of malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxyguanosine, as well as depressed antioxidants status, were observed in hepatic tissue of HCD fed rats. HCD induced abnormal elevation in the activities of hepatic lactate dehydrogenase, aminotransferases and alkaline phosphatase (ALP) and was accompanied by increased hepatic cholesterol level and altered fatty changes in the histology of liver. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats. The results of this study present oxidative injury induced by hypercholesterolemic diet and administration of the combination treatment of EPA-LA afforded sound protection against lipemic-oxidative injury.
Atherosclerosis 2006 Nov
PMID:Protective role of eicosapentaenoate-lipoate (EPA-LA) derivative in combating oxidative hepatocellular injury in hypercholesterolemic atherogenesis. 1645 14

Hypercholesterolemia, an independent risk factor for increased oxidative renal injury, is associated with the formation of oxidized low-density lipoprotein. Production of reactive oxygen species and nitrogen species have been implicated in diet-induced hypercholesterolemia, principally as means of oxidising low-density lipoproteins. This in turn initiates the accumulation of cholesterol in macrophages, which sets key event in the initiation of atherosclerosis. The aim of the present work is to evaluate the effects of eicosapentaenoic acid (EPA), DL alpha-lipoic acid (LA) and eicosapentaenoate-lipoate derivative (EPA-LA) in controlling the atherogenic disturbances. Four groups of male Wistar rats were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. Among them, 3 groups of rats were treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) from 16th day to 30th day of the experimental period. Abnormal increase in the levels of reactive oxygen species, 3-nitrotyrosine, malondialdehyde and protein carbonyl as well as an elevation in the activities of xanthine oxidase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase was observed in renal tissue of HCD fed rats. HCD fed rats also showed an increased susceptibility of the apo B-containing lipoproteins to in vitro oxidation. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats.
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PMID:Oxidative renal injury and lipoprotein oxidation in hypercholesterolemic atherogenesis: Role of eicosapentaenoate-lipoate (EPA-LA) derivative. 1673 4

Hydroxycut, an herbal supplement not currently defined as a drug, is frequently sold over the counter to increase exercise performance, build muscles, and burn fat. The effects of 8 wk of hydroxycut-induced changes on blood lipid profile in rats fed with either regular or high-fat diet were evaluated. Regardless of fat content in the diet, the doses of hydroxycut used significantly decreased fasting serum concentrations of cholesterol, triacylglycerol (TAG), low-density lipoprotein (LDL) cholesterol, total apolipoprotein B (apo B), and LDL/high-density lipoprotein (HDL) cholesterol ratio. A significant increase in serum blood glucose level was observed with hydroxycut intake in the presence of a high-fat diet. No hydroxycut-related changes in serum activities of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate dehydrogenase (SGPT), lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK) enzymes were noted, indicating no liver damage occurred. A decrease in liver fat content was observed with hydroxycut intake. The drug did not affect the number and composition of secreted very-low-density lipoprotein (VLDL) particles except for a decrease in VLDL TAG when the fat content in the diet was high. Hydroxycut reduced significantly LDL apo B and LDL TAG and cholesterol concentrations. Hydroxycut increased TAG and cholesterol excretion in feces. A single intragastric food load containing hydroxycut reduced significantly postprandial plasma TAG concentration in a dose-dependent manner. In conclusion, hydroxycut intake in recommended doses exerts a beneficial impact on atherosclerosis, an effect attributed to improved clearance and metabolism of lipoprotein particles, and to a lesser extent to an increased excretion of TAG and cholesterol in the feces. More studies are needed to ensure the safety of long-term use of hydroxycut.
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PMID:Effect of hydroxycut intake on fasted and postprandial lipemia in rats. 1685 87

Abnormal growth of vascular smooth muscle cells is seen in various pathological conditions such as hypertension, atherosclerosis, and restenosis. Na/H exchanger (NHE) activation appears to play a permissive role in vascular smooth muscle cell proliferation and vascular remodeling. The present study investigated the effect of a new specific NHE-1 inhibitor, sabiporide, on human pulmonary artery smooth muscle cell proliferation and migration. Concentrations of sabiporide as low as 20 micromol/L in the culture medium containing growth factors inhibited cell proliferation, as measured by cell counting, and also inhibited the rate of DNA synthesis, as examined by measuring BrdU incorporation into DNA. Cell growth inhibition was not caused by cell death, as demonstrated by the measurement of intracellular lactate dehydrogenase release and by the reversibility of inhibition upon washing. By fluorescent-activated cell sorting analysis, we are the first to demonstrate that NHE-1 inhibition arrests the cell cycle progression at G0/G1 phase, suggesting that NHE activation plays a permissive role in entrance of cells into the cell cycle. Sabiporide also concentration-dependently inhibited human pulmonary artery smooth muscle cell migration. The present study showed that sabiporide inhibits vascular smooth muscle cell proliferation and migration by blocking the cell cycle progression at G0/G1 phase.
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PMID:Inhibition of human pulmonary artery smooth muscle cell proliferation and migration by sabiporide, a new specific NHE-1 inhibitor. 1695 19


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