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)

Strategies aimed at treating atherosclerosis by immunization protocols are emerging. Such protocols commonly use adjuvants as non-specific stimulators of immune responses. However, adjuvants are known to modify various disease processes. The aim of this study was to determine whether adjuvants alter the development of atherosclerosis. We performed immunization protocols in apolipoprotein E knockout mice (E degrees ) following chronic administration schedules commonly employed in experimental atherosclerosis. Our results point out a dramatic effect of several adjuvants on the development of atherosclerosis; three of the four adjuvants tested reduced lesion size. The Alum adjuvant, which is the adjuvant currently used in most vaccination protocols in humans, displayed a strong atheroprotective effect. Mechanisms accounting for atheroprotective effect of Freund's adjuvants included their capacity to increase both Th2 responses and anti-MDA-LDL IgM titers, and/or to impose atheroprotective lipoprotein profiles. The present study indicates that adjuvants have potent atheromodulating capabilities, and thus, implies that the choice of adjuvant is crucial in long-term immunization protocols in experimental atherosclerosis.
Atherosclerosis 2006 Feb
PMID:Atheroprotective effect of adjuvants in apolipoprotein E knockout mice. 1605 Dec 52

Deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO production and increases reactive oxygen species. The purpose of this study was to elucidate the effects of aging on endothelial function and to determine whether the degree of BH4 deficiency is related to aging and oxidative stress. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after co-infusion of BH4 (500 mg/min) in 37 healthy men (mean age, 41+/-18 yr; range, 19-81 yr). FBF was measured using strain-gauge plethysmograph. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) were measured as indices of oxidative stress. Both ACh and ISDN increased the FBF in a dose-dependent manner in all subjects. Co-infusion of BH4 resulted in a significant increase in ACh-induced vasodilation (from 22.3+/-6.7 to 30.1+/-7.5 mL/min/100 mL tissue, P<0.05). Aging was found to be significantly correlated with ACh-induced vasodilation (r=-0.47, P=0.006), urinary 8-OHdG (r=0.38, P=0.02), serum MDA-LDL (r=0.36, P=0.02), and the change in ACh-induced vasodilation after co-infusion of BH4 (r=0.45, P=0.007). The FBF response to ISDN did not correlate with any parameters. Infusion of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, abolished the BH4-induced enhancement of forearm vasorelaxation evoked by ACh. The increase in FBF after ISDN was not altered by BH4. These findings suggest that a deficiency of BH4 may be involved in the pathogenesis of disturbances in endothelium-dependent vasodilation related to aging through decrease in NO production and increase in oxidative stress.
Atherosclerosis 2006 Jun
PMID:Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production. 1612 43

We hypothesized that a reduction in atherogenic malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels, which may antagonize the action of atheroprotective high-density lipoprotein cholesterol, leads to coronary plaque regression. This study investigated the effects of pravastatin on the serum levels of MDA-LDL and coronary atherosclerosis. In a 6-month prospective study, 75 patients with stable coronary artery disease were randomly assigned to a pravastatin-treatment group (n = 52) or a control group (n = 23). Volumetric analyses were performed in matched coronary artery segments by 3-dimensional intravascular ultrasound. Pravastatin therapy for 6 months resulted in a decrease in coronary plaque volume (14.4%, p <0.0001) and a corresponding reduction in serum MDA-LDL levels (12.7%, p = 0.0001). In the pravastatin treatment group, the percentage of change in plaque volume correlated with changes in the MDA-LDL and high-density lipoprotein cholesterol levels (r = 0.52 and -0.55, respectively, p <0.0001) but not with the changes in any other lipid levels. Multivariate regression analysis revealed that a reduced MDA-LDL level is an independent predictor of plaque regression, as was an increase in high-density lipoprotein cholesterol. In conclusion, these results suggest that the reduction in the MDA-LDL levels induced by pravastatin may serve as a novel marker of coronary atherosclerosis regression.
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PMID:Effect of pravastatin on malondialdehyde-modified low-density lipoprotein levels and coronary plaque regression as determined by three-dimensional intravascular ultrasound. 1621 43

Oxidized low-density lipoprotein cholesterol (Ox-LDL) is considered to play a critical role in the pathogenesis of atherosclerosis. We investigated the role of malondialdehyde-modified LDL (MDA-LDL), an indicator of Ox-LDL, in cerebral infarction. We also investigated the relationship between MDA-LDL and atherosclerotic change of the carotid artery. Subjects were 30 patients with lacunar infarction (LA), 19 patients with atherothrombotic infarction (AT) and 48 controls. Carotid arteries were evaluated with B-mode Doppler ultrasonography. The intima-media thickness (IMT) was considered to be increased if its value was more than 1.1 mm. The level of MDA-LDL concentration was significantly (P < 0.05) elevated in AT patients (129.96 +/- 27.88 U/I) than in LA patients (99.35 +/- 34.06 U/l) and controls (97.65 +/- 32.61 U/l). Among AT patients, plasma level of MDA-LDL concentration was statistically significantly elevated in the group with increased IMT (139.7 +/- 24.5 U/l) than in the group without increased IMT (102.7 +/- 17.2 U/l). No statistically significant difference was found among LA patients. However, there was no difference in LDL-C concentration between the patients with and without IMT thickening among LA or AT patients. The concentration of MDA-LDL was significantly decreased (P < 0.05) after statin administration for 5-6 months. MDA-LDL, namely degraded or qualitatively changed LDL-C, appears to be related to atherosclerotic change of the carotid artery in AT patients.
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PMID:Increase in plasma malondialdehyde-modified low-density lipoprotein in patients with atherothrombotic cerebral infarction. 1628 8

Capsaicin (8-methyl-N-vanillyl-6-nonemide) is the major pungent principle found in hot peppers of the plant genus Capsicum. The present work was undertaken to investigate the antioxidative property of capsaicin on markers of oxidative stress; membrane lipid peroxidation (formation of malondialdehyde) and membrane carbonyl groups in human erythrocytes. The effect of capsaicin has been compared with l-ascorbic acid. Subjecting erythrocytes to oxidative stress by incubating them with t-BHP caused a significant increase in MDA level and protein carbonyl group content above the basal value. The presence of capsaicin (10 microm) in the incubation medium protected the erythrocytes from t-BHP-induced oxidative stress as evidenced by the decrease in MDA level and protein carbonyl group content, l-ascorbic acid also showed similar protective effect. The results conclusively prove the efficacy of the antioxidant property of capsaicin. This evidence suggests that dietary factors that act as antioxidants to decrease membrane lipid peroxidation and protein carbonyl formation may contribute to a protective effect against cancer, atherosclerosis and age related diseases. This antioxidant effect may, in part, explain the high consumption of capsicum in certain regions of the world.
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PMID:Protection of lipid peroxidation and carbonyl formation in proteins by capsaicin in human erythrocytes subjected to oxidative stress. 1655 14

The interrelation was studied of processes of lipid peroxidation (LPO), the antioxidant system (AOS) with the level of endogenous intoxication (EI) during treatment with olbetam. Before the treatments administered, significantly high levels were recordable of LPO, EI against the background of low AOS activity. An one-month course of treatment with olbetam was found to be effective in all the parameters studied (LPO, AOS, EI). One month after the withdrawal of the drug the olbetam action on the AOS activity plasma level of MDA is still observable, with the processes of LPO and EI tending to return to normal. The abovestated permits recommending olbetam in the treatment of atherosclerosis obliterans of arteries of the inferior limbs as a hypolipidemic drug preparation endowed with an antioxidant and deintoxicationg activities.
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PMID:[Effects of olbetam on lipid reroxidation, the antioxidant system and endogenous intoxication in patients with atherosclerosis obliterans of arteries of the lower extermities]. 1678 59

Oxidized low-density lipoprotein (oxLDL) is a key autoantigen in atherosclerosis. The genetic structures and pathogenic roles of autoantibodies against this protein remain to be established. In this study, we cloned several monoclonal IgG autoantibody Fab fragments specific for oxLDL from peripheral blood lymphocytes of atherosclerosis patients, using phage display technology. The sequences of their variable regions were determined at the cDNA level. The closest germline counterparts for the heavy chains belonged to the V(H)3 or V(H)1 family. The sequences and lengths of complementarity-determining regions (CDR)3-V(H) were diverse, and frequent mutations of positively charged amino acids (particularly arginine) over entire V(H) and V(L) sequences were observed. It is proposed that anti-oxLDL autoantibody formation is driven by antigens. Among the Fabs, P2-8 and P3-175 bound to both MDA-LDL and Cu-oxLDL, and inhibited the uptake of oxLDL by macrophages, suggesting the epitope(s) recognized by the Fabs is a part of ligands on oxLDL that is involved in uptake by macrophage scavenger receptor. These human autoantibody Fabs require detailed investigation to ascertain their potential as agents for clinical applications.
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PMID:Characterization of human monoclonal autoantibody Fab fragments against oxidized LDL. 1679 38

Atherosclerosis is a disease associated with aging and is subject to modulation by both the innate and adaptive immune system. The time course of age-dependent changes in immune regulation in the context of atherosclerosis has not been characterized. This study aims to describe alteration of the immune responses to oxidized LDL (oxLDL) during aging that is associated with changes in plaque size and phenotype in apoE(-/-) mice. Mice fed a Western diet were euthanized at 15-17, 36, or >52 wk of age. The descending aortas were stained for assessment of extent of atherosclerosis. Plaque lipid, macrophage, and collagen content were evaluated in aortic sinus lesions. The adaptive immune response to oxLDL was assessed using anti-malondialdehyde-oxidized LDL (MDA-LDL) and copper-oxidized LDL (Cu-oxLDL) IgG, and the innate immune response was assessed using anti-Cu-oxLDL and phosphorylcholine (PC) IgM. Aging was associated with a significant increase in plaque area and collagen content and a decrease in plaque macrophage and lipid content. MDA-LDL IgG significantly increased at 36 wk but was reduced in mice >52 wk. Cu-oxLDL IgG increased with age and IgG-apoB immune complexes were increased in the >52 wk group. Cu-oxLDL and PC IgM significantly increased with age. The expression of splenic cytokines such as IFN-gamma, IL-4, and IL-10 increased with age. Our study shows a generalized increase in innate immune responses associated with progression of atherosclerosis and a less inflammatory and less lipid-containing plaque phenotype during aging. The adaptive immune response appeared to be less generalized, with a specific reduction in MDA-LDL IgG.
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PMID:Changes in immune responses to oxidized LDL epitopes during aging in hypercholesterolemic apoE(-/-) mice. 1682 16

Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum total cholesterol and LDL cholesterol levels resulting in increased risk for development of atherosclerosis. Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against infectious and degenerative diseases. Literature shows that the antioxidant activity is high in medicinal plants. Realizing the fact that, this study was carried out to determine the effect of ethanol extract of Hypericum lysimachioides Boiss var lysimachioides (Guttifera) on serum lipid levels and serum lipid peroxidation in hypercholesterolemic rabbits. The rabbits were divided into four groups and these groups were fed with diets containing standard laboratory diet (Group I), standard laboratory diet and ethanol extracts of H. lysimachioides (HL) (50mg/kg body weight) (Group II), standard laboratory diet, ethanol extracts of HL (50mg/kg body weight) and cholesterol (100mg/kg body weight) (Group III), and finally standard laboratory diet and cholesterol (100mg/kg body weight) (Group IV), for 5 weeks. Feeding cholesterol increased serum cholesterol and LDL cholesterol levels significantly in Group IV as compared to the other groups. Ethanol extract of HL with high cholesterol diet significantly lowered LDL cholesterol and total cholesterol levels in the rabbits of Group III as compared to the Group IV. The level of serum triacylglycerol was found to be similar to all comparison groups. HDL cholesterol levels were also increased significantly in Groups II and III as compared to Group IV. Statistically significant difference was found in Group IV as compared to all other groups. The ethanol extract of HL with high cholesterol diet significantly lowered the serum MDA levels in the rabbits of Group III compared to the Group IV. The histopathological findings confirmed that the ethanol extract of HL restrained the progression of the hydropic degeneration and fatty changes in the liver and some atherosclerotic lesions in the aorta. The in vitro antioxidant activities of ethanol extract of HL was also evaluated. The free radical-scavenging properties of HL (IC(50)=28 microg/ml) were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay system. Since plant phenolic compound is one of the phytochemicals possessing radical scavenging activity, the amount of total phenolic compound was also determined in ethanol extract of HL and total phenolic content of one-milligram HL ethanol extract was equivalent to 307 microg of gallic acid. Total antioxidant activity of ethanol extract of HL was tested by using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. Antioxidative activities of ethanol extract of HL was found to be comparable with Vitamin E. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.
Atherosclerosis 2007 May
PMID:The effect of ethanol extract of Hypericum lysimachioides on lipid profile in hypercholesterolemic rabbits and its in vitro antioxidant activity. 1690 89

Small low-density lipoprotein (LDL) particles and modifications to LDL such as glycation and oxidation have been linked to the pathogenesis of atherosclerosis in patients with diabetes. We investigated whether LDL particle size, or the levels of glycated LDL or malondialdehyde-modified LDL (MDA-LDL) are associated with carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus. One hundred seventy-two patients with type 2 diabetes mellitus were enrolled. Carotid IMT was measured by high-resolution ultrasound, and LDL particle size and serum glycated LDL and MDA-LDL levels were determined. The 3 variables were significantly correlated with one another. Univariate analyses defined statistically significant correlations of carotid IMT with LDL size, hemoglobin A(1c), glycated LDL, MDA-LDL, high-density lipoprotein (HDL) cholesterol, and age. The strongest association of IMT was with LDL size (r = -0.406, P < .0001), followed by that with HDL cholesterol (r = -0.225, P = .004). A stepwise multiple regression analysis revealed that LDL size and HDL cholesterol are independent predictors of carotid IMT. Neither glycated LDL nor MDA-LDL had a significant independent contribution to the severity of carotid IMT in the multivariate model. Low-density lipoprotein particle size, but not the glycated LDL or MDA-LDL level, was independently associated with carotid IMT in patients with type 2 diabetes mellitus regardless of antidiabetic and lipid-lowering medications. These results suggest that the measurement of LDL size may be more useful than quantification of modified LDLs for assessing atherosclerosis in patients with type 2 diabetes mellitus. Small LDL particles may be the most important predictor for the risk of cardiovascular disease in diabetic patients.
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PMID:Impact of low-density lipoprotein particle size on carotid intima-media thickness in patients with type 2 diabetes mellitus. 1744 34


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