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

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.
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PMID:Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury. 296 22

The variation in background radiation levels is an important source of information for estimating human risks associated with low-level exposure to ionizing radiation. Several studies conducted in the United States, correlating mortality rates for cancer with estimated background radiation levels, found an unexpected inverse relationship. Such results have been interpreted as suggesting that low levels of ionizing radiation may actually confer some benefit. An environmental factor strongly correlated with background radiation is altitude. Since there are important physiological adaptations associated with breathing thinner air, such changes may themselves influence risk. We therefore fit models that simultaneously incorporated altitude and background radiation as predictors of mortality. The negative correlations with background radiation seen for mortality from arteriosclerotic heart disease and cancers of the lung, the intestine, and the breast disappeared or became positive once altitude was included in the models. By contrast, the significant negative correlations with altitude persisted with adjustment for radiation. Interpretation of these results is problematic, but recent evidence implicating reactive forms of oxygen in carcinogenesis and atherosclerosis may be relevant. We conclude that the cancer correlational studies carried out in the United States using vital statistics data do not in themselves demonstrate a lack of carcinogenic effect of low radiation levels, and that reduced oxygen pressure of inspired air may be protective against certain causes of death.
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PMID:Altitude, radiation, and mortality from cancer and heart disease. 368 64

Male rats were fed a selenium-deficient Torula yeast diet with or without 0.2 ppm selenium (as sodium selenite) in the drinking water. Selenium deficiency caused a significant increase of urinary acetoacetate excretion in fed rats, and 24 or 48 hours of starvation enhanced this effect. Two days of selenium supplementation decreased the amount of urinary acetoacetate and 3-hydroxybutyrate to 50% of the deficiency value, indicating an enzymatic impairment in the selenium-deficient rat. No selenium-dependent effect was found for the following: (1) urinary pH, amount of nitrite, glucose (negative), hemoglobin or protein, and the urine was negative for phenylketones; (2) blood content of glucose, acetoacetate, or 3-hydroxybutyrate; or (3) liver content of glycogen, glucose, acetoacetate, or 3-hydroxybutyrate. On the other hand, the liver content of triglycerides was significantly lower in selenium deficiency. Indications for a higher content of ketone bodies (acetoacetate plus 3-hydroxybutyrate) in the kidneys from selenium-deficient rats were found. The increased urinary excretion of ketone bodies on selenium deficiency may indicate an impairment of lipid and ketone body turnover (in the kidney), or a decreased kidney reabsorption rate. Possible implications of these results in connection with protective roles of selenium in atherosclerosis and carcinogenesis are suggested.
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PMID:Impaired ketone body metabolism in the selenium deficient rat. Possible implications. 405 13

Atherosclerosis-susceptible White Carneau (WC-2) pigeons were compared with atherosclerosis-resistant Show Racer (SR-39) pigeons in terms of hepatic and aortic biotransformation and bioactivation of benzo[a]pyrene (B[a]P). Following pretreatment of the two strains with 3-methylcholanthrene (MC, 40 mg/kg), WC-2 hepatic 9000 X g supernatant fractions (S-9) exhibited consistently greater increases in the production of specific B[a]P metabolites when compared with uninduced controls than did the corresponding SR-39 preparations. Analyses of organic solvent-extractable metabolites with h.p.l.c. revealed that inducer pretreatment resulted in significantly greater increases (18- versus 7-fold) in the generation of B[a]P-7,8-dihydrodiol by WC-2 versus SR-39 hepatic S-9. Similar differences in inducibility were found for most other metabolites appearing in the h.p.l.c. profiles. Hepatic monooxygenase systems were induced in both strains following treatment of pigeons with a mixture of polychlorinated biphenyls (Aroclor 1254, 500 mg/kg); WC-2 birds again demonstrated greater responsiveness. Bioactivation of B[a]P to mutagenic (but not cytotoxic) products by hepatic S-9 was more effective in preparations from MC-pretreated WC-2 versus SR-39 pigeons when assessed with Salmonella typhimurium tester strains. Aortic homogenates from MC-pretreated pigeons displayed even greater inducibility differences than were observed with hepatic preparations. Inducer-mediated increases in the formation of B[a]P-7,8- and B[a]P-9,10-dihydrodiols were approximately 10- and 12-fold greater in WC-2 than SR-39 aortic preparations, respectively. The results document marked differences in biotransformation and bioactivation of carcinogenic hydrocarbons by atherosclerosis-susceptible and resistant pigeons and are reminiscent of the metabolic differences observed in carcinogenesis-susceptible and resistant strains of mice. It is suggested that these pigeon strains might offer a promising system in which to further study the role of target tissue biotransformation in the atherogenic actions of polynuclear aromatic hydrocarbons.
Carcinogenesis 1983
PMID:Carcinogenesis and atherogenesis: differences in monooxygenase inducibility and bioactivation of benzo[a]pyrene in aortic and hepatic tissues of atherosclerosis-susceptible versus resistant pigeons. 630 25

The evidence is reviewed that supports the role of genetic lesions in carcinogenesis; such lesions may be initiating events in the multistep process leading to clinically detectable tumor. Other possible manifestations of alterations in the hereditary material of somatic cells are discussed; DNA damage may lead to benign tumors responsible for atherosclerosis, to neurological deterioration, and to senescence of the individual. During embryonal development, transplacental mutagens may cause somatic mosaicism in the fetus, which may manifest as congenital malformations, spontaneous abortions, and childhood cancers.
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PMID:Somatic mutation theory. 746 28

Tumor necrosis factor alpha (TNF alpha), a pleiotrophic cytokine present in atherosclerotic lesions, caused a dose-dependent and persistent reduction in gap junctional intercellular communication (GJIC) between primary human smooth muscle cells in vitro. A continuous presence of TNF alpha was required for this persistent inhibition. Pretreatment of smooth muscle cells with ascorbic acid, alpha-tocopherol or glutathione prevented this inhibition of GJIC by TNF alpha. The persistent blockage of GJIC by continuous exposure to TNF alpha suggests that TNF alpha may share some mechanistic similarities with exogenous tumor promoters. Furthermore, this reduction in GJIC by TNF alpha may provide an additional link between the processes of atherosclerosis and carcinogenesis. The protection afforded by antioxidant compounds suggests a role for active oxygen species in the promotion stage of atherosclerosis.
Carcinogenesis 1995 Sep
PMID:Inhibition of gap junctional intercellular communication between primary human smooth muscle cells by tumor necrosis factor alpha. 755 55

Gangliosides suppress various immune activities in vitro and in vivo. Their level is significantly elevated in tumors and atherosclerotic aorta tissue, as well as in the sera of patients with tumors or atherosclerosis. Here, Lev Bergelson suggests that ganglioside-induced immunomodulation might be involved in atherogenesis and carcinogenesis, and describes a hypothesis that cites gangliosides as a factor interfering with the clearance of low-density lipoproteins (LDLs) and promoting the formation of atherosclerotic plaques.
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PMID:Serum gangliosides as endogenous immunomodulators. 757 52

Experimental carcinogenicity studies focus on identification of single carcinogens. Humans, however, appear exposed to a variety of low doses of carcinogens. Furthermore, few chemical entities are carcinogenic or toxic per se, but require metabolic activation to form ultimate carcinogens or toxins. In contrast to experimental animals, humans show considerable difference in genetic properties. In that situation it is particularly important to estimate individual capability for metabolic activation. To an increasing extent, activation includes formation of toxic oxygen metabolites. Particular targets for activated species are DNA and lipids; in particular low-density lipoproteins (LDL). Modifications of DNA are important for initiating the multistep process of carcinogenesis, in particular if oncogenes are activated or if tumor supressor genes are inactivated. Such DNA modification can be identical regardless of the reactive specimens being a xenobiotic or an oxygen species. Modification of LDL can start the process of atherosclerosis by transforming macrophages into foam cells, deposited as fatty streaks in the arterial wall. Biomarkers for activation capacity of xenobiotics include the use of prototype substrates and molecular techniques to determine genetic polymorphisms. Oxidative DNA modification can be measured from urinary excretion of oxidatively modified deoxynucleosides, particularly guanosine. Future efforts have to include individual measurements in order to improve the 'resolution' of molecular epidemiological approaches.
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PMID:Early biochemical markers of effects: enzyme induction, oncogene activation and markers of oxidative damage. 763 23

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural antioxidant defences have been found to be defective in many of the same diseases. This has led to suggestions that oxidative damage and therefore disease progression may be retarded by supplementing natural antioxidant defences. Potential antioxidant therapy includes natural antioxidant enzymes and vitamins or synthetic agents with antioxidant activity. Diseases where antioxidant therapy may be beneficial include diabetes mellitus, reperfusion injury, inflammatory diseases and the prevention of chronic processes such as atherosclerosis and carcinogenesis. Further well controlled prospective clinical trials of antioxidants are required to establish the efficacy and tolerability of antioxidant therapy in the treatment of human diseases.
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PMID:Prospects for the use of antioxidant therapies. 777 11

The authors subdued 183 vegetarians to examination, the aim of which was to judge the state of health and nutrition of the vegetarian population. The examined group was composed of people with their age ranging from 19-60 years, out of which 102 were of younger (19-39 years) and 81 were of older age. Their average period of vegetarian food consumption was 4.2 years. One third of men and a half of women were lacto-vegetarians, the rest were lacto-ovo-vegetarians. The results were compared with 160 nonvegetarians (64 of younger and 96 of older age). The detected values of lipid parameters were evaluated as favourable for vegetarians (low values of cholesterol, triacylglycerols, atherogenic index, LDL-cholesterol, the share of HDL-cholesterol was 28-33% (vs 24-26% in nonvegetarians) with values converging to 1.4 mmol.l-1--i.e. reduced risk). Additional favourable factors in prevention of atherosclerosis include the absence of obesity in vegetarians and values of antisclerotic active substances in blood (high values of vitamin C, in comparison with nonvegetarians a significantly higher molar ratio of vitamin E/cholesterol and vitamin E/triacylglycerols--more effective protection against peroxidation of lipids). Vegetarian mode of food consumption may be favourably evaluated regarding prooxidative-antioxidative parameters which play an important role in the process of atherogenesis, and carcinogenesis. Significantly lower values of conjugated dienes in plasma of vegetarians and vice versa high values of antioxidant substances (vitamin C, vitamin E/lipid components, catalase activity) were detected. A more pronounced system of detoxication in vegetarians is important due to a possible risk of an increased intake of xenogenous substances. (Tab. 3, Ref. 27.)
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PMID:[Lipid and pro-oxidative and antioxidative parameters in the blood of vegetarians]. 855 57


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