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

The purpose of this study was to determine whether the administration of Vitamin E (200 mg/day) for 4 weeks could decrease hypercholesterolemia and inhibit atherosclerosis in male hypercholesterolemic New Zealand White rabbits. Plasmatic Total Cholesterol (TC) and LDL-Cholesterol (LDLc) were determined by enzymatic methods and Vitamin E was determined in plasma by HPLC at weeks 0, 4 and 8. A histopathological study was carried out at week 8 (w 8), using a hematoxylin-eosin method. Forty rabbits were divided randomly into 5 groups and fed different diets. These diets included a Normal diet, a 1% Cholesterol rich diet, a Normal diet + Vitamin E and 1% Cholesterol rich diet + Vitamin E. The findings did not show a reduction of Total Cholesterol and LDLc in the groups of rabbits that received Vitamin E (III and IV) at weeks 4 and 8. At the end of the experiment, all the animals were deeply anesthetized with hydrochloride ketamina (60 mg/kg body wt) in order to carry out a histopathological study. Regarding the atherosclerotic lesions, Vitamin E did not induce inhibition of the atherosclerotic plaque development or any modification in the lesion type induced by the hypercholesterolemic diet. In conclusion, the results suggest that additional studies need to be carried out with higher doses and/or treatments for a longer period in order to clarify in detail whether Vitamin E really has a hypocholesterolemic effect and inhibits atherosclerosis.
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PMID:A study about the effect of vitamin E on hyperlipidemia and atherosclerotic lesions in New Zealand white rabbits fed with a 1% cholesterol rich diet. 1281 42

The 'oxidation theory' for atherosclerosis proposes that lipid and/or protein oxidation products are responsible for lesion formation/development. The major target for oxidation is suggested to be intimal low-density lipoprotein. This idea was stimulated by the pro-atherogenic properties of in vitro oxidized lipoproteins, such as stimulation of chemotaxis and sterol accumulation in macrophages, adhesion molecule expression on endothelial cells and apoptosis of several cell types. It was supported by detection of oxidation products in lesion lipoproteins, although these are (in general) less heavily oxidized and their biological activity is less rigorously defined than for their in vitro oxidized counterparts. Lesion lipids contain products generated by both enzymic and non-enzymic oxidation reactions; the majority are generated non-enzymically. The type and source of oxidant involved has been the subject of much speculation and is not resolved. The oxidation theory predicts that appropriate antioxidants will protect against atherosclerosis. Vitamin E has been used in several animal and human studies, but to date has shown little evidence of anti-atherosclerotic potential. However, lack of knowledge of the oxidant(s) driving lesion oxidation and the complexity of the anti- and pro-oxidant properties of vitamin E may explain its disappointing track record to date. These subjects require more rigorous study before the oxidation theory can be fairly tested.
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PMID:Lipid oxidation in atherogenesis: an overview. 1474 32

Cigarette smoking is known to promote atherosclerosis, possibly through enhanced oxidative stress. The aim of the present study was to elucidate the possible involvement of peroxynitrite in oxidative modification of low-density lipoprotein (LDL) induced by aqueous extract of cigarette smoke (CSE) and the preventive effect of fluvastain, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor with antioxidative activity, in vitro and in vivo. Modification of LDL was monitored by LDL subfraction analysis using anion-exchange HPLC, TBARS formation and 3-nitrotyrosine production. Incubation of LDL with CSE caused a marked increase in oxidative modification of LDL and nitration of tyrosine residues in the apolipoprotein B. These modifications were prevented by treatment with fluvastatin as well as Vitamin E in a concentration-related manner. Fluvastatin was equal to or more effective than Vitamin E for preventing protein nitration, but weaker for preventing oxidative modification. When CSE was injected daily into the ear vein of Watanabe heritable hyperlipidemic rabbits for 5 months, both oxidative modification and nitration of the plasma LDL noticeably occurred. These changes induced by CSE could be effectively prevented by the simultaneous oral administration of fluvastatin (10 and 30 mg/kg) or Vitamin E (150 mg/kg). Fluvastatin prevented the LDL nitration more effectively than Vitamin E. These results suggest that peroxynitrite in CSE is involved in oxidative modification of LDL and that fluvastatin can efficiently prevent LDL modification by scavenging peroxynitrite. Fluvastatin may be potentially beneficial to hypercholesterolemic patients with oxidative stress such as smoking.
Atherosclerosis 2004 Feb
PMID:Peroxynitrite-mediated oxidative modification of low-density lipoprotein by aqueous extracts of cigarette smoke and the preventive effect of fluvastatin. 1501 35

A corollary to the oxidation hypothesis of atherosclerosis is that the consumption of antioxidants is beneficial. However, the literature is divided in support of this conclusion. In this study, Boldine, an alkaloid of Peumus boldus and reduced form of RU486, was tested for their antioxidant potency both in, in vitro oxidation system and in mouse models. Boldine decreased the ex-vivo oxidation of low-density lipoprotein (LDL). Two different in vivo studies were performed to study the effect of these compounds on the atherosclerotic lesion formation in LDLR(-/-) mice. In study I, three groups of LDLR(-/-) mice (N = 12 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 and 3 were given 1mg of Boldine or Red RU per day for 12 weeks. In study II, two groups of LDLR(-/-) mice N = 10 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 was given 5mg of Boldine per day. The results indicated that there was a decrease in lesion formation reaching a 40% reduction due to Boldine and 45% reduction by Red RU compared to controls. The in vivo tolerance of Boldine in humans (has been used as an herbal medicine in other diseases) should make it an attractive alternative to Vitamin E.
Atherosclerosis 2004 Apr
PMID:A novel alkaloid antioxidant, Boldine and synthetic antioxidant, reduced form of RU486, inhibit the oxidation of LDL in-vitro and atherosclerosis in vivo in LDLR(-/-) mice. 1506 93

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
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PMID:Anti-atherosclerotic effects of vitamin E--myth or reality? 1509 Feb 61

Oxidant stress is a well known cause of damage in the atherosclerotic process. Vitamin E is one of the most promising natural antioxidants. In this study we investigated if a vitamin E-coated dialyzer was able to reduce the plasma levels of auto-antibodies against oxidized-LDL, von Willebrand factor (vWf) and thrombomodulin (TM) as markers of endothelial damage. In this controlled 6-month prospective study, we investigated these markers in two matched groups (n=16 each) of patients on regular hemodialysis not yet diagnosed for atherosclerosis cardiovascular disease (ACVD) (mean age=58.3+/-7.0 yrs, mean dialysis age=30.1+/-10.0 months), in which cellulosic (CLS) and vitamin E-modified dialyzers (CLE) were compared. At inclusion all the patients were treated with CLS. Then, the study group was shifted to CLE for 6 months. At baseline the patients showed normal levels of vitamin E and high levels of oxLDL-Ab, vWf and TM compared to healthy subjects. In the CLE group oxLDL-Ab and vWf, but not TM levels, decreased progressively (from 472+/-287 to 264+/-199 mU/mL, p<0.0001 and from 101.1+/-7.5% to 76.7+/-18.5%; p<0.001, respectively), and vitamin E increased from 4.40+/-0.81 to 7.81+/-1.16 microg/mg of cholesterol. At the end of the study, 8 of the patients treated with CLE were randomly selected and went back to the membrane without Vitamin E for six months. They showed an significant increase in OxLDL-Ab and vWf levels and a significant reduction in tocoferol levels. In conclusion, CLE compared to cellulosic dialyzers can lower some indices of damage to LDL and endothelial cells.
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PMID:Von Willebrand factor and autoantibodies against oxidized LDL in hemodialysis patients treated with vitamin E-modified dialyzers. 1511 87

Oxidative stress is involved in several pathological conditions, including diabetes. Reactive oxygen species (ROS) have been demonstrated to act as second messengers for several hormones and cytokines, including insulin (INS). The effect of Cu(2+)-oxidized LDL (CuLDL) on INS-induced generation of ROS and on INS signaling was investigated on cultured human fibroblasts. Intracellular ROS generation was observed either in CuLDL- or in INS-treated cells. Moreover, CuLDL and INS had an additive effect on ROS formation in human fibroblasts. CuLDL by itself increased the phosphorylation of ERK without affecting the PKB/Akt phosphorylation. CuLDL also stimulated the DNA binding activities of the transcription factors AP1 and NFkappaB. However, CuLDL dose-dependently prevented the INS-signaling pathway, by inhibiting the INS-induced phosphorylation of the signaling kinases ERK and PKB/Akt and the INS-induced activation of the transcription factors AP1 and NFkappaB. Finally, the lipophilic antioxidant Vitamin E (Vit E) partially restored all the studied signaling events initiated by INS and impaired after pretreatment with CuLDL. These studies demonstrate that the oxidative stress generated by CuLDL has a negative effect on the INS-signaling pathway, independently of the INS-induced generation of ROS. Thus, oxidized LDL might be involved not only in atherosclerosis, as it is commonly admitted, but also in the INS-resistance observed in type 2 diabetes mellitus.
Atherosclerosis 2004 Jul
PMID:Inhibition of insulin signaling by oxidized low density lipoprotein. Protective effect of the antioxidant Vitamin E. 1518 43

Suppression of cell adhesion molecule expression and macrophage accumulation by the endothelium is believed to play an important role in preventing the development of atherosclerosis. Earlier, we have shown that in vitro supplementation of human aortic endothelial cells with Vitamin E dose-dependently reduced expression of adhesion molecules and monocyte adhesion. Here, we report the in vivo down-regulation of endothelial cell adhesion molecules expression and macrophage accumulation in the aortas of hypercholesterolemic rabbits supplemented with Vitamin E. To this end, New Zealand White rabbits were fed a semi-purified diet containing 30 (control) or 1000 IU/kg Vitamin E. After 4 weeks, both groups' diets were switched to an atherogenic diet (0.3% cholesterol, 9% hydrogenated coconut oil, and 1% corn oil) containing the respective levels of Vitamin E and fed for 2, 4, and 6 weeks. Vitamin E supplemented rabbits had significantly higher levels of Vitamin E in their plasma and aortas. Frozen aorta sections were fixed and stained by an avidin-biotin complex method using Rb2/3 and Rb1/9 monoclonal antibodies against rabbit ICAM-1 and VCAM-1, respectively, and with RAM-11 for macrophage and von Willebrand factor for endothelial cells, followed by staining with secondary antibodies and counterstaining and evaluation under the microscope. At 6 weeks on atherogenic diet treatment, a trend (P = 0.08) toward a lower score of ICAM-1 expression by endothelial cells was observed in the aorta of Vitamin E treated rabbits compared to the control. However, a decrease in the score of VCAM-1 expression by endothelial cells in Vitamin E treated rabbits did not reach to a statistical significance. At 4 and 6 weeks on atherogenic diet, Vitamin E supplementation also significantly (P = 0.003) inhibited the accumulation of macrophages in the aorta. These results support the concept that down-regulation of adhesion molecule expression and suppression of monocyte/macrophage activation by Vitamin E in vivo is one of the potential mechanisms by which Vitamin E may suppress the development of aortic lesions in a rabbit model of atherosclerosis.
Atherosclerosis 2004 Oct
PMID:Vitamin E supplementation suppresses macrophage accumulation and endothelial cell expression of adhesion molecules in the aorta of hypercholesterolemic rabbits. 1538 Apr 48

Hyperhomocysteinemia is associated with decreased vascular reactivity and increased cardiovascular morbidity. Oxidative stress and reduced NO bioavailability have been proposed as a mechanism for the adverse effects of chronically elevated plasma homocysteine levels. Recent studies suggest that acute elevations of plasma homocysteine may also impair endothelial function and vasodilation, however, the mechanism is not clear. In the present study, we investigated whether moderate hyperhomocysteinemia after methionine loading decreases NO bioavailability, increases oxidative stress, and impairs receptor-mediated NO-dependent venodilation in healthy adults. After oral methionine loading (0.1g/kg), mean homocysteine concentrations increased 3.2-fold, from 6.9 +/- 0.5 to 27.8 +/- 1.9 micromol/l (n = 16), whereas plasma NO(x) concentrations, an indicator of NO release, were decreased by 12% compared to placebo treatment (P = 0.005). Vitamin E levels in freshly isolated low density lipoprotein (LDL), a sensitive marker of LDL oxidation, and LDL lipid (hydro)peroxide levels were unchanged after methionine loading. Endothelium-dependent venodilation induced by bradykinin was reduced by 18% during hyperhomocysteinemia (P = 0.06). Taken together our data suggest that the reduced NO bioavailability was likely due to decreased NO synthesis and release rather than to NO destruction by oxidative stress.
Atherosclerosis 2004 Oct
PMID:Acute hyperhomocysteinemia decreases NO bioavailability in healthy adults. 1577 62

Cardiovascular disease is the largest cause of mortality in hemodialysis patients. Cardiovascular mortality is fivefold to twentyfold higher in hemodialysis patients than in the general population. Atherosclerosis and vascular calcification are the characteristic complications in hemodialysis patients. Hemodialysis patients have traditional risk factors such as abnormal lipid metabolism and uremia-related risk factors such as oxidative stress and hyperphosphatemia. Oxidative stress takes place by increased production of oxidants by leukocytes and antioxidant loss of vitamin C and E. Oxidatively modified LDL exist in the circulation by excess of oxidative stress in hemodialysis patients. Oxidative stress is a major contributor to accelerated development atherosclerosis. Oxidative stress and hyperphosphatemia also influence vascular calcification. The pattern of vascular calcification in hemodialysis patient is characterized by mineral deposition in the tunica media. It is reported that the obvious calcification in aorta and artery of the MGP knockout mouse is recognized. It is indicated that MGP has the inhibitory effect of the calcification of vessel wall. Vitamin E protects atherosclerosis and vascular calcification in hemodialysis patients. It is also important to control hyperphosphatemia for vascular calcification.
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PMID:[Atherosclerosis and vascular calcification in hemodialysis patients]. 1557 60


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