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)

Women with diabetes mellitus are at high risk of myocardial infarction (MI), and it is well recognized that smoking, hypertension, hyperlipidaemia and the diabetic state itself do not fully explain this increased risk. During the last decade, growing evidence has accumulated that the immune system, with oxidized low-density lipoprotein (LDL) as a key antigen, plays an important role in the development of atherosclerosis. The aim of the present study was to explore the association between the immune response, as measured by antibody titres to malondialdehyde-treated LDL (MDA-LDL) and levels of C-reactive protein (CRP; a marker of inflammation), and diabetes mellitus and MI in women. Women (35-64 years) with diabetes (n=18) and non-diabetic women (n=46) who had been treated in hospital for MI were compared with diabetic women without MI (n=35) and healthy controls (n=70). Blood samples were collected after an overnight fast. CRP was determined with a highly sensitive immuno-enzymometric assay. IgM and IgG antibodies against MDA-LDL were analysed with a solid-phase ELISA technique. Women with diabetes but without previous MI were more similar to women with previous MI (both with and without diabetes) than to the healthy controls. Compared with healthy women, the women with diabetes and/or MI had higher IgG (P<0.05) and lower IgM (P=0.006) antibody titres against oxidized LDL and higher CRP levels (P<0.001), associations that were independent of other cardiovascular risk factors. These findings might indicate a differentiated immune response against modified LDL, more pronounced inflammation and a more aggressive atherosclerotic process in women with diabetes.
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PMID:Autoantibodies against oxidized low-density lipoprotein and C-reactive protein are associated with diabetes and myocardial infarction in women. 1167 58

Insulin resistance syndrome (IRS) is a cluster of prevalent conditions including glucose intolerance, hypertension and dyslipidemia, which commonly predispose to cardiovascular disease. However, the mechanism by which IRS is related with cardiovascular disease is not yet settled. Recently, it has been hypothesized that atherosclerosis is an inflammatory disease and that an increase in oxidative stress plays a key role in causing endothelial dysfunction associated with atherosclerosis. There has been, however, no study directly relating IRS with oxidative stress in human subjects. We measured various markers of oxidative stress among subjects who participated in a population-based epidemiological study performed in 1996. IRS was defined as non-diabetic subjects having more than two of three salient features of the syndrome (glucose intolerance, hypertriglyceridemia/low high density lipoprotein (HDL)-cholesterol and hypertension). The subjects with IRS (n=70) showed higher plasma malondialdehyde (MDA; 2.10+/-1.43 vs. 1.63+/-1.21 micromol/ml, P=0.009), homocysteine (16.32+/-8.34 vs. 13.06+/-6.49 micromol/l, P=0.002) and ceruloplasmin concentrations (29.80+/-5.28 vs. 27.39+/-5.10 mg/dl, P=0.002) than control subjects (n=196). Plasma MDA concentration was positively correlated with waist-to-hip ratio (r=0.124, P=0.044), and with plasma triglyceride (TG; r=0.163, P=0.008), ferritin (r=0.200, P=0.002) and homocysteine concentrations (r=0.136, P=0.032). These results suggest that increase in oxidative stress may contribute to the development of cardiovascular disease in IRS.
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PMID:Oxidative stress markers in Korean subjects with insulin resistance syndrome. 1173 6

Forty rats fed with basic diets were randomly divided into 4 groups. NG group were fed with basic diets. The other three groups were fed with high fat diets. The rats in TA group and EC group were given TA 100 mg/kg or EC 100 mg/kg each day respectively in addition to high fat diet for 8 weeks. The results showed that taurine and extraction of cristata L not only increased the level of red cell SOD and the content of serum Zn (P < 0.05), but also decreased the contents of TC, MDA in the wall of artery and decreased the level of serum LDH significantly (P < 0.05 or P < 0.01). TA and EC increased significantly the content of serum Cu and decreased the ratio of serum Cu to Zn in the high fat diet rats (P < 0.01), and decreased the contents of serum Ca also. The results indicate that TA and EC may play some role in lipid metabolism and inhibit atherosclerosis by regulating the levels of Zn, Cu and Ca in rats.
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PMID:[Effects of taurine and extraction of cristata L on serum Zn, Cu and Ca in rats]. 1193 54

Recent establishment of a sensitive ELISA system using antibodies against malondialdehyde-modified low density lipoprotein (MDA-LDL) made it possible to determine the circulating oxidized lipoprotein levels. Here, we investigated the serum levels of MDA-LDL in 62 patients with coronary artery disease (CAD) compared with the levels in 42 patients without CAD [groups CAD(+) and CAD(-), respectively], which are adjusted for age, serum total cholesterol, LDL and high density lipoprotein cholesterol, and triglyceride levels. Serum MDA-LDL levels were 113.4+/-49.1 IU/L in CAD(+), which were significantly higher than the levels in CAD(-) (85.2+/-22.5 IU/L, P<0.0005). The ratio of MDA-LDL/LDL cholesterol was 0.95+/-0.32 in CAD(+), indicating a significant increase compared with the ratio in CAD(-) (0.68+/-0.19, P<0.0005). The positive correlation of MDA-LDL level and the ratio of MDA-LDL/LDL cholesterol with intima-media thickness in carotid arteries was observed. Age was not clearly associated with the MDA-LDL level (P=0.865). The serum MDA level was positively correlated with LDL cholesterol (P<0.0001) and with triglycerides (P<0.001) and negatively correlated with high density lipoprotein cholesterol (P<0.05). Furthermore, the MDA-LDL level was negatively correlated with the peak size of the LDL particle (P<0.01). The LDL subclasses that were identified by using the sera collected from the subjects by sequential ultracentrifugation showed that the ratios of MDA-LDL/apolipoprotein B in LDL3 and LDL4 were nearly 3-fold higher than those in LDL1 and LDL2 for CAD(+) and CAD(-). These results indicate that the circulating MDA-LDL level is increased in CAD(+), independent of the serum LDL cholesterol level but in association with the peak size of LDL particles. The measurement of serum MDA-LDL level may be useful for the identification of patients with advanced atherosclerosis.
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PMID:Increased circulating malondialdehyde-modified LDL levels in patients with coronary artery diseases and their association with peak sizes of LDL particles. 1195 Jul 7

A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor is recommended in hemodialysis (HD) patients with hypercholesterolemia to improve their lipid profiles. We evaluated effects of simvastatin on markers for inflammation, oxidative stress, and coagulation in HD patients. Sixty-two maintenance HD patients with serum cholesterol levels of 200 mg/dL or greater were randomly assigned to the treatment group (n = 31; 8 men, 23 women; age, 63 +/- 11 years) and administered simvastatin, 20 mg/d, for 8 weeks or to the control group (n = 31; 10 men, 21 women; age, 60 +/- 12 years). We measured cholesterol, albumin, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA; an index of lipid peroxidation), and D-dimer (a marker of intravascular coagulation) in blood at baseline and again at 8 weeks. Fifty-eight of 62 patients completed the study. In the control group, total cholesterol, serum albumin, hs-CRP, MDA, and D-dimer levels did not change. In the treatment group, simvastatin administration for 8 weeks significantly reduced total cholesterol levels from 232 +/- 25 to 165 +/- 39 mg/dL (P < 0.001) and hs-CRP levels from a median of 0.23 mg/dL (range, 0.05 to 1.63 mg/dL) to 0.12 mg/dL (range, <0.006 to 1.45 mg/dL; P < 0.01), whereas it increased serum albumin levels from 3.4 +/- 0.3 to 3.6 +/- 0.4 g/dL (P < 0.001). Administration of simvastatin did not affect MDA and D-dimer levels. These results suggest that in addition to the lipid-lowering effect, simvastatin had an antiinflammatory effect in HD patients. Considering that atherosclerosis is inflammation of the vascular wall, simvastatin may have a beneficial effect on cardiovascular disease, in part because it alleviates inflammation.
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PMID:Effects of simvastatin on high-sensitivity C-reactive protein and serum albumin in hemodialysis patients. 1204 33

Connective tissue growth factor (CTGF) is a 38-kd protein involved in several human fibrotic disorders including atherosclerosis and skin and renal fibrosis. Although it has been shown that human and experimental liver fibrosis is associated with CTGF expression through up-regulation of CTGF mRNA by hepatic stellate cells (HSC), the role of CTGF in the liver has not yet been determined. The aim of the present study was to assess the effects of CTGF on rat primary HSC and its regulation in a well-established model of in vitro liver fibrogenesis. Incubation of primary HSC with recombinant CTGF induced a significant migratory (2.3-fold, 50 ng/ml CTGF) and proliferative effect (1.8-fold, 100 ng/ml CTGF). Type I collagen mRNA expression, as assessed by a real-time RT-PCR procedure, was also increased when cells were incubated in the presence of CTGF (2-fold, 50 ng/ml). Transforming growth factor-beta1 (TGF-beta1) strongly stimulated CTGF mRNA expression, a direct mechanism observed in the absence of any intermediate protein synthesis. Furthermore, spontaneous activation of HSC plated on plastic and stimulation by vascular endothelial growth factor, lipid peroxidation products (HNE, MDA), acetaldehyde, and platelet-derived growth factor (PDGF)-BB significantly up-regulated CTGF mRNA expression in HSC. PDGF-induced CTGF stimulation might be related in part to TGF-beta1 secretion because CTGF mRNA up-regulation observed after PDGF-BB stimulation was abrogated in the presence of neutralizing TGF-beta1 antibody. In conclusion, this study extends the role of CTGF in HSC activation and suggests that CTGF up-regulation might be a central pathway during HSC activation.
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PMID:Effects and regulation of connective tissue growth factor on hepatic stellate cells. 1206 87

Previous studies have demonstrated that low density lipoprotein (LDL) enriched in polyunsaturated fatty acids (PUFA) are more susceptible to oxidation (ex vivo) than those containing monounsaturated fatty acids (MUFA). To test whether this observation was associated with various parameters considered to be related with the development of early aortic atherosclerosis, hamsters were fed commercial hypercholesterolemic diets (HCD) containing either the PUFA, sunflower oil (SF) or the MUFA, TriSun oil (TS) at 10% with 0.4% cholesterol (wt/wt). LDL isolated from hamsters fed TS had significantly longer lag phase (30%, P < 0.05), a decreased propagation phase (-62%, P < 0.005), and fewer conjugated dienes formed (-37%, P < 0.007) compared to hamsters fed SF. Aortic vasomotor function, measured as degree of aortic relaxation, was significantly greater in the TS vs SF-fed hamsters whether acetylcholine or the calcium ionophore A23187 was used as the endothelium-dependent agonist. As a group, the SF-fed hamsters had significantly more early atherosclerosis than hamsters fed TS (46%, P < 0.006). When animals across the two diets were pair-matched by plasma LDL-C levels, there was an 82% greater mean difference (P < 0.002) in early atherosclerosis in the SF versus the TS-fed hamsters. While there were no significant associations with plasma lipids and lipoprotein cholesterol, early atherosclerosis was significantly correlated with lag phase (r = -0.67, p < 0.02), rate of LDL conjugated diene formation (r = 0.74, p < 0.006) and maximum dienes formed (r = 0.67, p < 0.02). Compared to TS-fed animals, aortic sections from hamsters fed the SF-containing diet revealed that the cytoplasm of numerous foam cells in the subendothelial space reacted positively with the monoclonal anti-bodies MDA-2 and NA59 antibody, epitopes found on oxidized forms of LDL. The present study suggests that compared to TS, hamsters fed the SF-diet demonstrated enhanced LDL oxidative susceptibility, reduced aortic relaxation, greater early aortic atherosclerosis and accumulation of epitopes found on oxidized forms of LDL.
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PMID:Decreased aortic early atherosclerosis in hypercholesterolemic hamsters fed oleic acid-rich TriSun oil compared to linoleic acid-rich sunflower oil. 1212 26

Oxidised low-density lipoprotein (LDL) has physicochemical properties that are pivotal in atherosclerotic plaque formation. As a consequence, antioxidant regimens may prove an important therapy in the prevention and treatment of cardiovascular disease. Since oxidised LDL is immunogenic, the aims of our study were to measure serum IgG titres to malondialdehyde-modified LDL (MDA-LDL) in patients with coronary artery disease (CAD) and control subjects and assess their potential as a clinical marker for coronary atherosclerosis and, consequently, antioxidant intervention. Serum IgG titres to MDA-LDL were measured in patients with angiographically confirmed CAD (n = 40) and aged-matched controls (n = 40) by enzyme-linked immunosorbant assay (ELISA). Titres were calculated and expressed as both the difference and the ratio of blanked absorbance units (AU) for IgG binding to MDA-LDL and native LDL. For the control population, median IgG titres were 0.26 AU (interquartile range (IQR) 0.20-0.46 AU) and 5.34 (IQR 3.40-8.58), respectively, while the patient population had median IgG titres of 0.30 AU (IQR 0.20-0.47 AU) and 5.08 (IQR 3.30-9.66), respectively. Both sets of calculated titre values were not significantly different between the two groups (P = 0.60 and 0.82, respectively). In conclusion, this study could not establish any significant association between circulating autoantibody titres to MDA-LDL and coronary atherosclerosis. Therefore, the diagnostic value of autoantibodies to oxidised LDL remains unclear.
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PMID:Autoantibodies to malondialdehyde-modified low-density lipoprotein in patients with angiographically confirmed coronary artery disease. 1254 95

Numerous studies have indicated that the oxidative modification of low-density lipoprotein (LDL) plays a critical role in the pathogenesis of atherosclerosis. Malondialdehyde-modified LDL (MDA-LDL) is one of the candidate oxidative products. Therefore, to allow the assessment of oxidized LDL in human serum, we developed monoclonal antibodies for MDA-LDL. Two of these-MDA1 and MDA2-bound to oxidized LDL but not to native LDL by Western blot analysis. The murine monoclonal antibodies to oxidized LDL have potential clinical implications, as imaging agents, for defining the compositions of atherosclerotic vessels in vivo.
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PMID:Generation and characterization of IgG monoclonal antibodies specific for malondialdehyde. 1451 71

Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) is a risk factor for cardiovascular diseases (CVD). Oxidative stress mechanisms are often reported to be implied in type 2 diabetes mellitus. In order to determine their clinical relevance, we investigated several plasma indicators in the Turkish patients with NIDDM: (i) homocysteine (Hcy) and cysteine (Cys) which contribute to increase the risk of atherosclerosis during NIDDM, (ii) glutathione (GSH) and cysteinylglycine (CysGly) resulting from GSH degradation catalyzed by gamma-glutamylcysteine transferase (GGT), (iii) malonaldehyde (MDA) as a marker for lipid peroxidation, and (iv) total antioxidant status (TAS). Our main results were evaluated based on sex and diabetic status. In female patients, plasma concentrations of MDA and Hcy were significantly higher than in controls, while GSH levels were significantly lower. In males, a difference between control and diabetic groups was noticed only for Hcy, levels being also higher in patients. In the diabetic group, increase in serum glucose concentration was significantly correlated with increased GGT activity. In both controls and diabetic patients, GGT activity was correlated with a raised Cys concentration and a decreased GSH level. In both controls and diabetic patients, there were significant positive correlations between Cys and Hcy and between GSH and Hcy. We concluded that GSH and MDA levels are clinical indicators for an oxidative process linked to type 2 diabetes mellitus, especially in women.
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PMID:Thiols, malonaldehyde and total antioxidant status in the Turkish patients with type 2 diabetes mellitus. 1464 36


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