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)

Endothelial injury is important in the pathogenesis of thrombosis, atherosclerosis, disseminated intravascular coagulation, and vasculitis. The ability of several common human viruses to infect cultures of endothelial cells obtained from human umbilical veins or bovine thoracic aorta was demonstrated. Indicators of infection included cytopathology, viral growth curves, and antigen detection by immunofluorescence. Herpes simplex virus type 1, adenovirus type 7, measles virus, and parainfluenza virus type 3 infected both human venous and bovine aorta endothelium. Mumps virus, poliovirus type 1, and echovirus type 9 grew only in human venous cells; coxsackievirus B4 infected only bovine arterial cultures; and cytomegalovirus, influenza A/Victoria/75 (H3N2) virus, and respiratory syncytial virus failed to grow in either cell culture. During replication some viruses caused acute lytic changes; some produced chronic, less destructive alterations; and other induced no apparent cytopathology. The results suggest that viral replication within endothelium may be important in the pathogenesis of viral disease of initiation of vessel-wall injury.
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PMID:Virus infection of endothelial cells. 626 Aug 74

Reactive oxygen intermediates (ROI) such as superoxide (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (.OH) are involved in the pathogenicity of various diseases. There is also evidence that superoxide is involved in disease progression following infection by influenza virus, HIV-1 and human cytomegalovirus (HCMV). Healthy donor-derived peripheral blood monocytes/macrophages, which seem to be the major reservoir for HCMV in vivo, showed significantly higher generation of O2- after HCMV infection. The importance of O2- in cytomegalovirus pneumonitis was also supported in a mouse model system using mouse cytomegalovirus. In addition, the importance of HCMV-induced ROI was also shown in the restenosis and atherosclerosis of smooth muscle cells. This review highlights the relationship between HCMV infection and ROI.
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PMID:[Superoxide generation and human cytomegalovirus infection]. 946 68

This paper evaluates the current information on the relationship between oral disease (specifically periodontitis) and atherosclerosis/coronary heart disease (CHD) to determine whether the information is sufficient to conclude that periodontitis is a risk factor for atherosclerosis/CHD. As background for this evaluation, the term "risk factor" is defined, and the 3 criteria used to establish exposures as risk factors are reviewed. In addition, epidemiologic criteria for defining an exposure as causal are presented. The available evidence then is evaluated according to the criteria for causality, which are extensions of the criteria for establishing a risk factor. This review is done in the context of the relationship between atherosclerosis/CHD and inflammation. A number of findings are briefly reviewed that link inflammation and atherosclerosis/CHD, such as: 1) prior flu-like symptoms were more common in cases of myocardial infarction than in concurrently sampled controls; 2) high levels of cytomegalovirus antibody titers were associated with elevated carotid intimal-medial wall thickness 18 years later; 3) prior infection with cytomegalovirus was a strong independent risk factor for restenosis after coronary atherectomy; 4) dental infections were more common in cases of cerebral infarction compared to community controls matched on age and sex; and 5) the gingival index was significantly correlated with fibrinogen and white cell counts in periodontal patients and controls, adjusted for age, smoking, and socioeconomic status. Three case-control studies and 5 longitudinal studies investigating the relationship between dental conditions and atherosclerosis/CHD are reviewed in terms of strength of associations, consistency of associations, specificity. of associations, time sequence between exposure and outcome, and degree of exposure and outcome. Related to the last criterion, new findings are presented which indicate that the extent of the periodontal infection, a measure reflecting microbial burden, also is related to onset of new CHD events. Our previously published model describing the potential biological mechanisms underlying the associations found is reviewed. This model places the associations into a context of an intrinsic or acquired hyperinflammatory monocyte trait that results in a more intense inflammatory response to lipopolysaccharide (LPS) challenges, such as periodontal infections. This hyperinflammatory response may promote atheroma formation and thromboembolic events. finally, new findings from ongoing animal studies are presented, indicating that high fat diets in atherosclerotic-susceptible mice induce greater inflammatory responses to Porphyromonas gingivalis challenges. We conclude that the available evidence does allow an interpretation of periodontitis being a risk factor for atherosclerosis/CHD. This conclusion, however. is made with some qualifications. While the associations found across a wide variety of subjects are remarkably consistent, for the most part they are represented by incidence odds ratios around 2.0. While this level of association would result in oral conditions contributing to a large number of CHD cases, it is possible that associations of this magnitude are due to bias in the study designs. In addition, some studies report that periodontitis is associated with all-cause mortality and low birth weight infants. These multiple associations detract from the credibility of periodontitis as a risk factor, as specificity of association is more often related to causality. However, all-cause mortality may largely be driven by mortality from cardiovascular events: and some exposures, such as smoking. are indeed risk factors for multiple conditions. On the other hand, current findings regarding the associations between oral conditions and atherosclerosis/CHD imply that the criteria for causality may be met in the not-too-distant future.
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PMID:Periodontitis: a risk factor for coronary heart disease? 972 97

The impact of diet and specific food groups on aging and age-associated degenerative diseases has been widely recognized in recent years. The modern concept of the free radical theory of aging takes as its basis a shift in the antioxidant/prooxidant balance that leads to increased oxidative stress, dysregulation of cellular function, and aging. In the context of this theory, antioxidants can influence the primary "intrinsic" aging process as well as several secondary age-associated pathological processes. For the latter, several epidemiological and clinical studies have revealed potential roles for dietary antioxidants in the age-associated decline of immune function and the reduction of risk of morbidity and mortality from cancer and heart disease. We reported that long-term supplementation with vitamin E enhances immune function in aged animals and elderly subjects. We have also found that the beneficial effect of vitamin E in the reduction of risk of atherosclerosis is, in part, associated with molecular modulation of the interaction of immune and endothelial cells. Even though the effects of dietary antioxidants on aging have been mostly observed in relation to age-associated diseases, the effects cannot be totally separated from those related to the intrinsic aging process. For modulation of the aging process by antioxidants, earlier reports have indicated that antioxidant feeding increased the median life span of mice to some extent. To further delineate the effect of dietary antioxidants on aging and longevity, middle-aged (18 mo) C57BL/6NIA male mice were fed ad libitum semisynthetic AIN-76 diets supplemented with different antioxidants (vitamin E, glutathione, melatonin, and strawberry extract). We found that dietary antioxidants had no effect on the pathological outcome or on mean and maximum life span of the mice, which was observed despite the reduced level of lipid peroxidation products, 4-hydroxynonenol, in the liver of animals supplemented with vitamin E and strawberry extract (1.34 +/- 0.4 and 1.6 +/- 0.5 nmol/g, respectively) compared to animals fed the control diet (2.35 +/- 1.4 nmol/g). However, vitamin E-supplemented mice had significantly lower lung viral levels following influenza infection, a viral challenge associated with oxidative stress. These and other observations indicate that, at present, the effects of dietary antioxidants are mainly demonstrated in connection with age-associated diseases in which oxidative stress appears to be intimately involved. Further studies are needed to determine the effect of antioxidant supplementation on longevity in the context of moderate caloric restriction.
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PMID:The effect of long-term dietary supplementation with antioxidants. 992 43

Rural health care delivery is often inferior to that of urban areas. Although health services do not have to be identical in the two settings, quality services appropriate for the needs of rural communities are imperative. Moreover, health education and promotion should be seen as an immediate and viable strategy for (a) reducing risk factors and health care needs, and (b) increasing the cost effectiveness of existing services. The appropriateness and prioritization of health care services and health education/promotion can only be realized if health professionals are aware of rural versus urban needs. To facilitate our knowledge of such differences, the mortality rates of the 10 leading causes of death were compared for each county in Ohio and differences between rural and urban mortality were analyzed. Counties were categorized according to "density" (persons per square mile) and "percent urban" (percent of county area classified as urban). The analysis demonstrated that there were no significant differences between rural and urban counties in mortality due to cancer, pulmonary disease, diabetes mellitus, atherosclerosis, and suicide. Mortality related to cardiovascular disease, cerebrovascular disease, accidents, and influenza/pneumonia was significantly higher in rural counties, while deaths due to chronic liver disease were significantly greater in urban counties.
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PMID:Difference in rural and urban mortality: implications for health education and promotion. 1029 26

1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low-density lipoprotein (LDL) from oxidation. We functionally evaluated the anti-oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations. 2. After native LDL (N-LDL) from rabbit plasma had been pre-incubated in the presence or absence of fluvastatin (10 micromol/L) for 4 h, the N-LDL was mildly oxidized by incubation with 5 micromol/L CuCl2 for 5 h and two oxidized LDL, fluvastatin-pretreated (Flu-OxLDL) and -non-treated (OxLDL), were prepared. The level of thiobarbituric acid-reactive substances (TBARS) in Flu-OxLDL and OxLDL markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 3. When macrophages were incubated with Flu-OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 4. Acetylcholine-induced endothelium-dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu-OxLDL or OxLDL. The degree of impairment was significantly less in Flu-OxLDL. 5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium-dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 micromol/L). 6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti-oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.
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PMID:Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta. 1083 Dec 43

Oxidative stress is implicated in the pathogenesis of atherosclerosis, and of viral infections caused by sendai virus, influenza and HIV. Vascular oxidative stress is due to inflammatory and immune responses of vascular cells, and to reperfusion after recanalization of blocked arteries. Because human cytomegalovirus (CMV) may contribute to atherogenesis by several mechanisms, and coronary artery smooth muscle cells (SMC) are permissive for the virus, we examined CMV interactions with SMC. Infection causes generation of intracellular reactive oxygen species (ROS) which activate NF-kappa B, a cellular transcription factor. NF-kappa B mediates expression of the CMV promoter and of genes involved in the immune and inflammatory responses. Antioxidants or aspirin inhibit ROS, NF-kappa B and CMV.
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PMID:Cytomegalovirus gene regulation by reactive oxygen species. Agents in atherosclerosis. 1086 53

Oxidation of low density lipoprotein (LDL) phospholipids containing arachidonic acid at the sn-2 position occurs when a critical concentration of "seeding molecules" derived from the lipoxygenase pathway is reached in LDL. When this critical concentration is reached, the nonenzymatic oxidation of LDL phospholipids produces a series of biologically active, oxidized phospholipids that mediate the cellular events seen in the developing fatty streak. Normal high density lipoprotein (HDL) contains at least 4 enzymes as well as apolipoproteins that can prevent the formation of the LDL-derived oxidized phospholipids or inactivate them after they are formed. In the sense that normal HDL can prevent the formation of or inactivate these inflammatory LDL-derived oxidized phospholipids, normal HDL is anti-inflammatory. HDL from mice that are genetically predisposed to diet-induced atherosclerosis became proinflammatory when the mice are fed an atherogenic diet, injected with LDL-derived oxidized phospholipids, or infected with influenza A virus. Mice that were genetically engineered to be hyperlipidemic on a chow diet and patients with coronary atherosclerosis, despite normal lipid levels, also had proinflammatory HDL. It is proposed that LDL-derived oxidized phospholipids and HDL may be part of a system of nonspecific innate immunity and that the detection of proinflammatory HDL may be a useful marker of susceptibility to atherosclerosis.
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PMID:HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. 1130 61

Macrophage-derived apolipoprotein E (apoE) influences the susceptibility of the arterial wall to atherosclerosis. Previous studies have shown that production of apoE in these cells is regulated at a posttranscriptional level and is increased by inhibitors of proteasomal degradation. To further investigate this mechanism, we stably transfected RAW 264.7 macrophages and HepG2 cells with a construct overexpressing ubiquitin, the peptide targeting proteins to the proteasome, fused to an influenza virus hemagglutinin epitope tag. Ubiquitination of apoE was investigated by immunoprecipitation and Western blot analysis. In both cell types, apoE was ubiquitinated, and inhibition of proteasome function by lactacystin led to accumulation of ubiquitinated apoE. These studies provide strong evidence for proteasomal degradation of apoE in the two main cell types responsible for its production and indicate a possible new level of regulation of this important protein.
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PMID:Apolipoprotein E in macrophages and hepatocytes is eegraded via the proteasomal pathway. 1140 4

Infectious agents, in particular intracellular pathogens that can establish long-term, persistent seropositivity, may play an important role in atherogenesis. The possible association between influenza type A and B infection and angiographically proven coronary artery disease (CAD) and the effect of the aggregate pathogen burden on CAD was studied by testing blood from 218 patients undergoing coronary angiography for serum IgG antibodies to influenza A and B, and for antibodies to four other pathogens (hepatitis A, Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus). This analysis demonstrates that although influenza (A and B) seropositivity represents no predictor of risk for CAD, infectious burden is independently associated with coronary atherosclerosis.
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PMID:Influenza A and B IgG seropositivity and coronary atherosclerosis assessed by angiography. 1244 Oct 11


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