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

Vitamin E is the most effective lipid-soluble antioxidant present in mammalian cells. The hypothesis that links vitamin E to atherogenesis postulates that oxidative modifications of unsaturated fatty acids in the low-density lipoprotein particles play a crucial role in the pathogenesis of this chronic disease. Therefore, vitamin E supplementation should reduce the extent of oxidation and, thus, be protective against atherosclerosis. This hypothesis is strongly supported by studies in murine models of atherosclerosis. In contrast, clinical trials using this vitamin have been giving a more confused picture than expected, with results ranging from a significant protective action to the absence of any effect. However, these findings do not reduce the validity of the "oxidative hypothesis" and of the large body of experimental evidence accumulated so far in its favor. Several differences between animal studies and clinical trials, and among clinical trials themselves are taken into account in order to explain the conflicting findings. Finally, insights into what might be the most appropriate nature of future trials in humans are given.
 ...
PMID:Vitamin E: murine studies versus clinical trials. 1183 31

Experimental and clinical evidence suggest that angiotensin converting enzyme (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting endothelial dysfunction, atherosclerosis and thrombus formation. These direct effects are in addition to effects on vascular tone or pressure. The Health Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who were at high risk of CV events but did not have left ventricular dysfunction, heart failure, or high blood pressure at the time of study entry. In the overall HOPE population, the risk of the primary composite outcome (cardiovascular death, myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004). Ramipril treatment achieved risk reduction in patients with mild renal insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not increase adverse events in patients with renal insufficiency. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of carotid intimal medial thickening, suggesting a direct effect on atherosclerotic progression.
 ...
PMID:What should the role of ACE inhibitors be in the treatment of diabetes? Lessons from HOPE and MICRO-HOPE. 1184 51

We have previously shown that tetradecylthioacetic acid (TTA), a sulfur containing saturated fatty acid analogue, inhibits the oxidative modification of human low-density lipoprotein (LDL) in vitro. The oxidative modification of LDL is believed to be a crucial step in the progression of atherosclerosis. In the present study, we investigated the effect of TTA oral administration on the susceptibility of rat lipoprotein to undergo oxidative modification ex vivo. Lipoprotein resistance to copper-induced oxidation was highly improved after TTA administration to rats. Conjugated dienes produced after 150 min of lipoprotein oxidation were dramatically lowered in the TTA treated rats compared to controls. Malondialdehyde and lipid peroxides production by oxidation was highly limited. These effects were independent of any Vitamin E effects. More than 50% relative reduction in polyunsaturated fatty acids of the n-3 family, and more than 30% relative increase in 18:1n-9 fatty acid in the triacylglycerol (TAG)-rich lipoprotein were observed. TAG-rich lipoprotein lipids of TTA fed rats were decreased with more than 50% reduction in TAG. The data reported in this paper indicate a potent in vivo antioxidant capability of TTA that beside its hypolipidemic effect might be of importance in relation to the development of atherosclerosis.
 ...
PMID:Inhibition of rat lipoprotein oxidation after tetradecylthioacetic acid feeding. 1193 45

Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary disease and also inhibits the proliferation of VSMCs in vitro. We used vitamin E and probucol to treat glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two animal models of glomerular disease. Using rats, a remnant kidney model accelerated with hyperlipidemia was employed to reflect progressive glomerular sclerosis leading to chronic renal failure, and an anti-thymocyte serum treatment was used to model acute MC-proliferative GN. Supplemental dietary antioxidants suppress MC proliferation and glomerular sclerosis in models of glomerular disease in rats. These results suggest that treatment with antioxidants may be a promising intervention to prevent progression of kidney disease.
 ...
PMID:Effects of antioxidants on kidney disease. 1204 53

We used the apolipoprotein E deficient (apo e-/-) mice to analyze the role of macrophage reduced glutathione (GSH) content in cell-mediated oxidation of LDL and in atherosclerotic lesion development. Apo e-/- mice were supplemented with L-2-oxo-4-thiazolidin carboxylate (OTC, which supplies cysteine residues, 500 mg/kg/day), or with buthionine sulfoximine (BSO, a specific inhibitor of GSH synthesis, 400 mg/kg/day) for 6 weeks. Then mouse peritoneal macrophages (MPM) and the mice aortas were collected. MPM from apo e-/- mice contained decreased GSH levels (by 58%), and a four-fold increased lipid peroxides content compared to control macrophages from C57BL6 mice. These MPM demonstrated increased capability to release superoxide anions and to oxidize LDL in comparison to control MPM. OTC supplementation resulted in a 26% increase in macrophage GSH, paralleled by a 25% reduction in cellular lipid peroxides content. Decrement by 30% in superoxide anion release and LDL oxidation by MPM, and also in the atherosclerotic lesion size by 25%, was found in the OTC-treated mice, compared to placebo-treated apo e-/- mice. In contrast, in BSO-treated mice MPM a further depletion of cellular GSH by 22% was found, paralleled by a two-fold increase in lipid peroxides content, and a 41% increased superoxide anion release and cell-mediated LDL oxidation, compared to placebo-treated apo e-/- mice MPM. Most important, BSO supplementation to apo e-/- mice caused a 59% increase in the atherosclerotic lesion area. An additional way to increase cellular GSH content was the use of dietary antioxidants. Vitamin E (40 mg/kg/day) or the isoflavan glabridin (25 microg/kg/day) administration for 2 months to apo e-/- mice resulted in the accumulation of these antioxidants in their MPM, and increased MPM GSH content by 24 and 80%, respectively. MPM lipid peroxides content was reduced by 31 or 60% upon vitamin E or glabridin supplementation, paralleled by a 30 or 60% decrease in cell-mediated oxidation of LDL, respectively. Finally, a significant inverse correlation (R=0.83) was found between macrophage GSH content and cell-mediated oxidation of LDL. We conclude that enrichment in vivo of macrophages with GSH, significantly decreases cellular oxidative stress, leading to reduced capability of the macrophages to oxidize LDL, and hence GSH may attenuate the development of atherosclerosis.
Atherosclerosis 2002 Jul
PMID:Increased macrophage glutathione content reduces cell-mediated oxidation of LDL and atherosclerosis in apolipoprotein E-deficient mice. 1204 18

Up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and reduced nitric oxide (NO) availability represent early characteristics of atherosclerosis. To evaluate whether the antioxidant vitamin E affected the circulating levels of soluble VCAM-1 (sVCAM-1) and the plasma metabolite of NO (nitrite+nitrate) in hypercholesterolemic patients, either vitamin E (either 400 IU or 800 IU/d for 8 wk) or placebo were randomly, double-blindly given to 36 hypercholesterolemic patients and 22 age- and sex-matched controls. At baseline hypercholesterolemic patients showed higher plasma sVCAM-1 (microg.liter(-1)) (591.2 +/- 132.5 vs. 505.0 +/- 65.6, P < 0.007) and lower NO metabolite (microM) levels (15.9 +/- 3.4 vs. 29.2 +/- 5.1, P < 0.0001) than controls. In hypercholesterolemic patients, 8 wk vitamin E (but not placebo) treatment significantly decreased circulating sVCAM-1 levels (400 IU: -148.9 +/- 84.6, P < 0.009; 800 IU: -204.0 +/- 75.7, P < 0.0001; placebo: -4.7 +/- 22.6, NS), whereas it increased NO metabolite concentrations (400 IU: +4.0 +/- 1.7, P < 0.02; 800 IU: +5.5 +/- 0.8, P < 0.0001; placebo: +0.1 +/- 1.1, NS) without affecting circulating low- density lipoprotein levels. Changes in both plasma sVCAM-1 and NO metabolite levels showed a trend to significantly correlate (r = -0.515, P = 0.010; and r = 0.435, P = 0.034, respectively) with changes in vitamin E concentrations induced by vitamin E supplementation. In conclusion, isolated hypercholesterolemia both increased circulating sVCAM-1 and reduced NO metabolite concentrations. Vitamin E supplementation counteracts these alterations, thus representing a potential tool for endothelial protection in hypercholesterolemic patients.
 ...
PMID:Vitamin E supplementation reduces plasma vascular cell adhesion molecule-1 and von Willebrand factor levels and increases nitric oxide concentrations in hypercholesterolemic patients. 1205 Feb 77

Oxidation of low-density lipoproteins constitutes the first step of a very complex process leading to atherosclerosis. Vitamin E, and principally a-tocopherol, is considered as the principal inhibitor of lipid peroxidation. Some studies showed the beneficial role of vitamin E in the prevention and reduction of atherosclerosis and its associated pathologies. However, other in vitro studies advance a prooxidant role of vitamin E. The results of the epidemiologic studies are difficult to generalize without taking account of the clinical randomized tests. In this work, we reviewed the principal studies devoted to the role of vitamin E and discussed the assumption of a prooxidant effect of this molecule.
 ...
PMID:[Molecular mechanisms of the protective effect of vitamin e against atherosclerosis]. 1218 19

Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilisation. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of alpha-tocotrienol vitamin E.
 ...
PMID:Vitamin E in cardiovascular disease: has the die been cast? 1249 32

Inflammatory and oxidative stresses play a pivotal role in atherogenesis. Vitamin E and vitamin C are the two most important dietary antioxidants; moreover, vitamin E has anti-inflammatory effects. Combined supplementations with vitamin E and vitamin C twice daily for 3 y reduced lipid peroxidation and retarded the progression of common carotid atherosclerosis in healthy men in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. To further elucidate the underlying mechanisms that retarded the progression of atherosclerosis in the ASAP study, we investigated the effect of a combined intake of vitamin E and vitamin C on inflammatory markers in vivo. Circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C reactive protein (CRP) were measured in 45- to 69-y-old men from the ASAP study with cholesterol >5.0 mmol/L before and after treatment with either placebo (n = 52) or a combined supplementation with 91 mg (136 IU) alpha-tocopherol and 250 mg of slow-release vitamin C twice a day (n = 55) for 3 y. Antioxidant treatment for 36 mo had no effect on circulating levels of TNF-alpha, IL-6 or CRP. In conclusion, long-term combined supplementations with alpha-tocopherol and vitamin C in reasonable doses have no detectable systemic anti-inflammatory effects in a healthy population of men with slight hypercholesterolemia and no overt signs of inflammation.
 ...
PMID:Long-term combined supplementations with alpha-tocopherol and vitamin C have no detectable anti-inflammatory effects in healthy men. 1267 38

Epidemiological and biochemical studies infer that oxidative processes, including the oxidation of low-density lipoprotein (LDL), are involved in atherosclerosis. Vitamin E has been the focus of several large supplemental studies of cardiovascular disease, yet its potential to attenuate or even prevent atherosclerosis has not been realised. The scientific rationale for vitamin E supplements protecting against atherosclerosis is based primarily on the oxidation theory of atherosclerosis, the assumption that vitamin E becomes depleted as disease progresses, and the expectation that vitamin E prevents the oxidation of LDL in vivo and atherogenic events linked to such oxidation. However, it is increasingly clear that the balance between vitamin E and other antioxidants may be crucial for in vivo antioxidant protection, that vitamin E is only minimally oxidised and not deficient in atherosclerotic lesions, and that vitamin E is not effective against two-electron oxidants that are increasingly implicated in both early and later stages of the disease. It also remains unclear as to whether oxidation plays a bystander or a casual role in atherosclerosis. This lack of knowledge may explain the ambivalence of vitamin E and other antioxidant supplementation in atherosclerosis.
 ...
PMID:The role of vitamin E in atherosclerosis. 1281 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>