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)

Selenium is an essential trace element that is an integral part of many proteins, with catalytic and structural functions. The antioxidant properties of some selenoproteins, such as glutathione peroxidase, may be particularly important in carcinogenesis and heart disease. The content of selenium in food depends on the selenium content of the soil where the plants are grown or the animals are raised. Moreover, the metabolism of selenium is determined by its dietary form: some forms are better utilized than others. Therefore, wide variations have been found in selenium status in different parts of the world. In animal studies, selenium deficiency is associated with cardiomyopathy and sudden death, as well as reduced T-cell counts and impaired lymphocyte proliferation and responsiveness. Abnormalities in liver function, brain, heart, striated muscle, pancreas and genital tract have also been reported. In humans, selenium deficiency has been implicated in the etiology of cardiovascular disease and other conditions in which oxidative stress and inflammation are prominent features, but there is still only limited evidence from epidemiological and ecological studies for this, and the therapeutic benefit of selenium administration in the prevention and treatment of cardiovascular diseases remains insufficiently documented. Interventions studies are currently in progress to assess the benefits of selenium supplements in primary and secondary prevention of atherosclerosis. The results to date are inconclusive and further controlled trials are needed.
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PMID:The controversy surrounding selenium and cardiovascular disease: a review of the evidence. 1255 53

Low density lipoprotein has been shown to induce vascular smooth muscle cell proliferation and, therefore, to directly contribute to the development of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors involved in various cellular processes, such as cell cycle regulation and carcinogenesis. PPARgamma, the best characterized of the PPARs, plays a crucial role in the regulation of cell proliferation, adipocyte differentiation, insulin sensitivity, energy expenditure, development of atherosclerosis and carcinogenesis. In the present review we discuss recent findings showing that a new class of antidiabetic drugs, the PPARgamma ligands thiazolidinediones, might have potential antiatherosclerotic effects. (c) 2002 Prous Science. All rights reserved.
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PMID:Inhibition of the Low Density Lipoprotein-Induced Vascular Smooth Muscle Cell Growth by PPARgamma Ligands. 1267 38

Werner syndrome (WS) is a hallmark premature aging disease, in which the patients appear much older than their chronological age, and exhibit many of the clinical signs and symptoms of normal aging at an early stage in life. They develop many age-associated diseases early in life including atherosclerosis, osteoporosis, cataracts and display a high incidence of cancer. WS is also marked by increased genomic instability, manifested as chromosomal alterations. Characterization and study of the Werner protein (WRN) suggests that it participates in several important DNA metabolic pathways, and that its primary function may be in DNA repair processes. Thus, the WRN protein represents an important link between defective DNA repair and the processes related to aging and cancer.
Carcinogenesis 2003 May
PMID:Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. 1277 Oct 22

Peroxisome proliferator activated receptors (PPAR) belong to a family of nuclear receptors broadly distributed in the organism. Their pleiotropic role has been recently proved as well as their pathogenic significance in diabetes, obesity, cell cycle controlling, carcinogenesis, inflammation and atherosclerosis. The three types of PPAR identified until today have different tissue localization. PPARgamma, primarily identified in macrophages and adipocytes, play an important role in the expression of proteins essential for lipid metabolism and adipogenesis. PPARalpha are localized predominantly in hepatocytes and have also an important role in lipid metabolism. PPAR are though to be lipid sensors in organism. Carbohydrate metabolism is also under the control of PPAR and their exogenous ligands, (ie: thiasolidinediones), are important antidiabetic drugs.
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PMID:[Peroxisome proliferator activated receptors PPARs: their role in carbohydrate and lipid metabolism]. 1280 6

Advanced stages of both cancer and atherosclerosis are characterized by a local increase in tissue mass that may be hard to control. This increase in tissue mass can be attributed to oxidation-sensitive modification of cell cycle-related events, including cellular proliferation, differentiation, and apoptosis, which could be secondary to alteration in the activity of tumor suppressor gene and oncogene products. The oncogene c-Myc has classically been considered to be involved in carcinogenesis and has more recently been implicated in both endothelial dysfunction and atherogenesis as well. Consequently, inhibition of c-Myc-dependent signaling has become a novel therapeutic opportunity and challenge in atherosclerosis and other cardiovascular diseases. Antioxidant strategies, RNA synthesis inhibitors such as mithramycin, and gene therapeutic approaches with antisense oligonucleotides against c-Myc are some of the promising strategies. In general, the increased biologic understanding of the participation of cell cycle events and targeting these events may enable to attenuate or prevent some of the complications of vascular and neoplastic diseases.
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PMID:c-Myc oncoprotein: cell cycle-related events and new therapeutic challenges in cancer and cardiovascular diseases. 1285 83

Epidemiological and experimental studies suggest that antioxidants like vitamin E (alpha-tocopherol) may play an important role in prevention of chronic disease. Several observational surveys have linked populations with a large intake of vitamin E with reduced incidence of heart disease. These observations have been strengthened by the demonstration of strong antioxidant activity by vitamin E in cellular, molecular and animal experiments. These results have highlighted a potential role for vitamin E supplementation in the prevention of chronic disease in humans. Interestingly however, large-scale clinical trials of vitamin E and other antioxidants in preventing specific disease processes (e.g., coronary artery disease) have generated conflicting and mixed outcomes. In this review, the role of vitamin E in the prevention of atherosclerosis and carcinogenesis has been carefully examined with particular emphasis on salient human studies (clinical trials) and their limitations. In addition, pertinent biochemical, physiological and metabolic features of vitamin E have also been incorporated. A list of common natural food sources of vitamin E has been provided. Important in vitro and animal studies related to the antiatherosclerotic and anticarcinogenic actions of vitamin E have been discussed in detail. Finally, the direction of future investigations in primary and secondary prevention of chronic diseases by vitamin E supplementation has been outlined.
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PMID:Vitamin E and its role in the prevention of atherosclerosis and carcinogenesis: a review. 1289 39

Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.
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PMID:Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. 1291 Oct 45

Recent developments in biomedical science have shown that free radicals are involved in many diseases. They attack the unsaturated fatty acids in the biomembrane resulting in membrane lipid peroxidation, which is strongly connected to aging, carcinogenesis and atherosclerosis. Free radicals also attack DNA and cause mutation leading to cancer. In addition lipid peroxidation is an important factor of deterioration in the processing and storage of food. Therefore, it is important to search for new effective radical scavengers (Sci. Rev. 2 (1997) 152; J. Nat. Prod. Rev. 63 (2000) 1035). In this manuscript we describe the antioxidant activity of new thioureidic compounds.
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PMID:Antioxidant activity of thioureidic derivatives I. 1367 75

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon with atherogenic and carcinogenic properties. The role of B[a]P in carcinogenesis is well established, and thought to exert via enzymatic activation into reactive metabolites that are capable of binding to the DNA leading to uncontrolled proliferation. However, the mechanism underlying the atherogenic properties of B[a]P is still unclear. Therefore, the effects of chronic B[a]P exposure on atherosclerotic plaque development in apolipoprotein E knockout (apoE-KO) mice were studied. ApoE-KO mice were orally treated with 5 mg/kg/bw B[a]P once per week for 12 or 24 consecutive weeks. Levels of reactive B[a]P metabolites in the arterial tree (from the aortic arch until the iliac artery bifurcations) were high as shown by the level of B[a]P DNA-binding products measured in DNA isolated from the entire aorta (38.9 +/- 4.8 adducts/10(8) nucleotides). Analysis of atherosclerotic lesions in the aortic arch showed no influence of B[a]P on location or number of lesions. Moreover, no increased levels of p53 nuclear protein accumulation or cell proliferation, as detected by immunohistochemistry, were seen in the plaques of the B[a]P-exposed animals. However, the effects of B[a]P on advanced lesions were obvious: advanced plaques were larger and more prone to lipid core development and plaque layering at both 12 and 24 weeks (P < 0.05). In the B[a]P-exposed animals advanced plaques contained more T-lymphocytes and macrophages than in the control animals at both end points (P < 0.05). These data suggest that B[a]P does not initiate atherosclerosis in apoE-KO mice, but accelerates the progression of atherosclerotic plaques via a local inflammatory response.
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PMID:Chronic exposure to the carcinogenic compound benzo[a]pyrene induces larger and phenotypically different atherosclerotic plaques in ApoE-knockout mice. 1469 24

Dehydroepiandrosterone (DHEA) is an abundantly produced adrenal steroid whose biological role has never been clarified. DHEA is a potent uncompetitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH) and as a consequence lowers NADPH levels and reduces NADPH-dependent oxygen-free radical production. Overproduction of oxygen-free radicals, or oxidative stress, upregulates inflammation and cellular proliferation and is believed to play a critical role in the development of cancer, atherosclerosis, and Alzheimer's disease, as well as the basic aging process. Both in vitro and in vivo experimental studies strongly indicate that DHEA and related steroids inhibit inflammation and associated epithelial hyperplasia, carcinogenesis, and atherosclerosis, at least in part, through the inhibition of G6PDH and oxygen-free radical formation. Recent epidemiological findings in Sardinian males bearing the Mediterranean variant of G6PDH deficiency are consistent with the hypothesis that reduced G6PDH activity has a beneficial effect on age-related disease development and longevity. Clinical trials with DHEA are encumbered by the high oral doses required as well as the conversion of DHEA into active androgens. The use of less androgenic congeners as well as non-oral formulations may facilitate testing of this class of compounds.
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PMID:Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. 1517 53


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