Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome, although it is not known whether markers of NAFLD, including elevated concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK), predict the development of metabolic syndrome. Our objective was to investigate the associations of elevated AST, ALT, and other liver markers, including C-reactive protein (CRP), with incident National Cholesterol Education Program-defined metabolic syndrome among 633 subjects in the Insulin Resistance Atherosclerosis Study who were free of metabolic syndrome at baseline. Insulin sensitivity (Si) and acute insulin response (AIR) were directly measured from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. After 5.2 years, 127 individuals had developed metabolic syndrome. In separate logistic regression models adjusting for age, sex, ethnicity, clinic, and alcohol consumption, subjects in the upper quartiles of ALT, ALK, and CRP were at significantly increased risk of incident metabolic syndrome compared with those in the lowest quartile: ALT, odds ratio 2.50 (95% CI 1.38-4.51); ALK, 2.28 (1.24-4.20); and CRP, 1.33 (1.09-1.63). Subjects in the upper quartile of the AST-to-ALT ratio were at significantly reduced metabolic syndrome risk (0.40 [0.22-0.74]). After further adjustment for waist circumference, Si, AIR, and impaired glucose tolerance, the associations of ALT and the AST-to-ALT ratio with incident metabolic syndrome remained significant (ALT, 2.12 [1.10-4.09]; the AST-to-ALT ratio, 0.48 [0.25-0.95]). These associations were not modified by ethnicity or sex, and they remained significant after exclusion of former and heavy drinkers. In conclusion, NAFLD markers ALT and the AST-to-ALT ratio predict metabolic syndrome independently of potential confounding variables, including directly measured Si and AIR.
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PMID:Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. 1624 37

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

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P <.05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P <.05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P <.05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).
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PMID:Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes. 1655 57

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

Stent restenosis remains the main limitation of percutaneous coronary intervention. Elevated serum gamma-glutamyl transferase (GGT) level is associated with an inflammatory response. We aimed to determine the correlation of stent restenosis with the serums level of GGT. One hundred and twenty patients (age 58.56+/-10.46 years, 66% male) with a history of coronary stent implantation and had undergone control coronary angiography (60 with restenosis and 60 without) were included. All had baseline serum GGT activity and were free of systemic and hepatobiliary disease. Median baseline serum GGT activity was significantly higher in patients with restenosis (34.00 U/L (24.00-47.75)) than in those without restenosis (21.00 U/L (17.25-26.7500)) (P<0.0001). Stent restenosis was identified in 38% of the patients with a serum GGT value >40 U/L and in 5% of patients with a serum GGT value <or=40 U/L (P<0.001). Serum C-reactive protein (CRP) and total bilirubin levels were significantly higher (P=0.011 and 0.037, respectively) and alkaline phosphatase levels were significantly lower in patients with restenosis (P=0.029). Levels of GGT, CRP, and alkaline phosphatase were independent predictors of restenosis (P=0.001, 0.019 and 0.004, respectively). In conclusion, the serum level of GGT may be an independent marker for stent restenosis.
Atherosclerosis 2007 Dec
PMID:Serum gamma-glutamyl transferase activity: a new marker for stent restenosis? 1728 53

Hypercholesterolemia plays an important role in the initiation and progression of atherosclerosis and has a positive correlation with cardiovascular disease. Calcification is a common feature of atherosclerotic lesions and contributes to cardiovascular dysfunctions. The present study investigated the role of hypercholesterolemia in vascular calcification and its potential mechanism. Models of vascular calcification were established by administering vitamin D2 (VD) to rats alone or combined with a high-cholesterol diet (HCD) and by treating rat aorta smooth muscle cells (RASMCs) with beta-glycerophosphate (GP) alone or combined with oxidized low-density lipoprotein (oxLDL) in vitro. In rats, the combination of VD with HCD significantly enhanced vessel calcium deposition and the activity and mRNA expression of vessel alkaline phosphatase (ALP) compared to treatment with VD alone. This combination also enhanced serum levels of total cholesterol, oxLDL, and malondialdehyde as well as vascular production of superoxide anion, while it reduced the vascular activity of superoxide dismutase. Both simvastatin, a cholesterol-lowering agent, and antioxidant vitamin E antagonized the effects of the above combination. In RASMCs, oxLDL accumulation dependently accelerated calcium deposition in cell layers initiated by GP alone. Also, oxLDL stimulated ALP activity and mRNA expression in RASMCs in a concentration-dependent manner. Taken together, these results suggest that acceleration of vascular calcification by hypercholesterolemia might be attributed to oxidative stress and such calcification may be another target of statin or antioxidant action in antiatherosclerosis.
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PMID:Hypercholesterolemia accelerates vascular calcification induced by excessive vitamin D via oxidative stress. 1712 Jan 85

Numerous studies document that melatonin possesses a broad-spectrum antioxidant activity. It traps a number of reactive oxygen species (ROS) such as hydroxyl and peroxyl radicals, singlet oxygen and hypochlorous acid. It also inhibits peroxynitrite-induced reactions. It is known that atherosclerosis progression involves ROS-induced oxidation of low-density lipoproteins in sub-endothelial space and the depletion of nitric oxide (NO) in blood vessels, as well as a decreased sensitivity of the vessels to the actions of NO. Considering this, a series of new NO-donor antioxidants were designed and synthesized by joining melatonin with NO-donor nitrooxy and furoxan moieties as polyvalent agents potentially useful for the treatment of cardiovascular diseases involving atherosclerotic vascular changes. The in vitro antioxidant properties of the resulting products were assessed in the thiobarbituric acid reactive substances assay (TBARS), the ABTS(+.) as well as in the alkaline phosphatase (ALP) assay. The antioxidant capacities of NO-donor melatonins to inhibit lipoperoxidation (TBARS-IC(50)) was predominantly dependent on their lipophilicity, and therefore on their partitioning process into membranes. On the other hand, their comparable capacity to inhibit protein oxidation (ALP-IC(50)) was independent of their lipophilicity and was consistent with their similar ability to participate in electron transfer reactions. All the NO-donor melatonins were also evaluated for their ability to relax rat aorta strips precontracted with 1 microM phenylephrine. Finally, binding affinities and intrinsic activity studies, carried out at MT(1) and MT(2) receptor subtypes, showed a rather complex picture in need of further investigation.
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PMID:NO-donor melatonin derivatives: synthesis and in vitro pharmacological characterization. 1743 54

Cardiovascular disease, such as atherosclerosis, has been associated with reduced bone mineral density and fracture risk. A major etiologic factor in atherogenesis is believed to be oxidized phospholipids. We previously found that these phospholipids inhibit spontaneous osteogenic differentiation of marrow stromal cells, suggesting that they may account for the clinical link between atherosclerosis and osteoporosis. Currently, anabolic agents that promote bone formation are increasingly used as a new treatment for osteoporosis. It is not known, however, whether atherogenic phospholipids alter the effects of bone anabolic agents, such as bone morphogenetic protein (BMP)-2 and parathyroid hormone (PTH). Therefore we investigated the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on osteogenic signaling induced by BMP-2 and PTH in MC3T3-E1 cells. Results showed that ox-PAPC attenuated BMP-2 induction of osteogenic markers alkaline phosphatase and osteocalcin. Ox-PAPC also inhibited both spontaneous and BMP-induced expression of PTH receptor. Consistently, pretreatment of cells with ox-PAPC inhibited PTH-induced cAMP production and expression of immediate early genes Nurr1 and IL-6. Results from immunofluorescence and Western blot analyses showed that inhibitory effects of ox-PAPC on BMP-2 signaling were associated with inhibition of SMAD 1/5/8 but not p38-MAPK activation. These effects appear to be due to ox-PAPC activation of the ERK pathway, as the ERK inhibitor PD98059 reversed ox-PAPC inhibitory effects on BMP-2-induced alkaline phosphatase activity, osteocalcin expression, and SMAD activation. These results suggest that atherogenic lipids inhibit osteogenic signaling induced by BMP-2 and PTH, raising the possibility that hyperlipidemia and atherogenic phospholipids may interfere with anabolic therapy.
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PMID:Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts. 1752 49

Medial arterial calcification is a common finding in subjects with diabetes mellitus. In vitro, glucose or insulin supplementations promote a phenotypic shift of smooth muscle cells into osteogenic cells, but the mechanisms driving this conversion are poorly understood. The binomial hyperglycaemia/hyperinsulinemia is typical of insulin resistance states, in which the metabolic and vasomotor ("good") actions of insulin are selectively impaired, whereas its mitogenic ("bad") signals are potently enhanced. Under these conditions, insulin can exert pro-atherosclerotic effects and promote vascular calcification. In this setting, the metabolic and mitogenic pathways may be not entirely antagonist, because they interact to traduce the normal insulin signal into inhibition of calcification. Emerging data suggest that the two pathways may converge on the regulation of phosphate transport and extracellular inorganic phosphate (Pi) concentrations. Two antagonist enzymes governing Pi metabolism are alkaline phosphatase (ALP) and the ectonucleotide pyrophosphatase/phosphodiesterase-1 (also known as PC-1): while ALP is up-regulated in calcified diabetic arteries, PC-1 is also implicated in the genesis of insulin resistance. Therefore, we suggest that the functional interactions between ALP and PC-1 may link insulin resistance to vascular calcification.
Atherosclerosis 2007 Aug
PMID:The good and the bad in the link between insulin resistance and vascular calcification. 1760 64

S100A8 and S100A9 are calcium-binding proteins expressed in myeloid cells and are markers of numerous inflammatory diseases in humans. S100A9 has been associated with dystrophic calcification in human atherosclerosis. Here we demonstrate S100A8 and S100A9 expression in murine and human bone and cartilage cells. Only S100A8 was seen in preosteogenic cells whereas osteoblasts had variable, but generally weak expression of both proteins. In keeping with their reported high-mRNA expression, S100A8 and S100A9 were prominent in osteoclasts. S100A8 was expressed in alkaline phosphatase-positive hypertrophic chondrocytes, but not in proliferating chondrocytes within the growth plate where the cartilaginous matrix was calcifying. S100A9 was only evident in the invading vascular osteogenic tissue penetrating the degenerating chondrocytic zone adjacent to the primary spongiosa, where S100A8 was also expressed. Whilst, S100A8 has been shown to be associated with osteoblast differentiation, both S100A8 and S100A9 may contribute to calcification of the cartilage matrix and its replacement with trabecular bone, and to regulation of redox in bone resorption.
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PMID:S100A8/S100A9 and their association with cartilage and bone. 1763 30


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