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

Atherosclerosis (AR) is the leading cause of morbidity and mortality in the US and cigarette smoking is a major contributing factor to the disease. Like cigarette smoking in lung cancer, genetic susceptibility may be an important factor in determining who is more likely to develop AR. However, the current emphasis has been on susceptibility based on altered cardiovascular homeostasis. In this investigation, we studied 120 AR patients and 90 matched controls to elucidate the association between polymorphisms in some metabolizing genes (GSTM1, GSTT1, CYP2E1, mEH, PON1, and MPO) and susceptibility to AR. We found that the GSTT1 null allele and the fast allele of mEH(*) (exon 4) are associated with risk for AR. Furthermore, the combined genotypes GSTM1 null/ CYP2E1(*)5B, GSTM1 null/mEH YY, and GSTT1 null/mEH YY are significantly associated with susceptibility to AR (OR = 15.42, 95% CI = 1.33-77.93, P = 0.021; OR = 3.48, 95% CI = 1.63-8.04, P = 0.0008; OR = 3.4; 95% CI = 0.99-17.38, P = 0.05; respectively). We have also conducted cytogenetic analysis to elucidate if induction of chromosome aberrations (CAs) is a biomarker of AR susceptibility. We found that among cigarette smokers (AR patients and smoker controls), individuals having the GSTM1 null allele had a significantly higher frequency of CAs compared to those with the normal allele (P < 0.05). This association was not found among nonsmokers. In addition, individuals who had inherited the CYP2E1(*)5B allele exhibited a significantly higher CA frequency (8.0 +/- 0.82) compared to those with the CYP2E1 wild-type genotype (4.31 +/- 0.35). Since the analysis of genetic susceptibility factors is still in its infancy, our study may stimulate additional investigations to understand the roles of genetic susceptibility and cigarette smoking in AR.
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PMID:Polymorphic metabolizing genes and susceptibility to atherosclerosis among cigarette smokers. 1235 48

Atherosclerotic changes in aortas and coronary arteries of victims of cancer were investigated within framework of 2 epidemiological studies of men aged 20-59 years in Malmo, Prague, Riga, Tallin, Yalta and of women aged 40-59 years in Malmo, Riga and Yalta conducted in 1963-1966 (first study) and 1985-1989 (second study) years. The first study included 763 men and 419 women and the second - 744 men and 293 women with malignancies. Control group comprised practically healthy victims of accidents. Extent of atherosclerosis depended on localization of cancer. Compared with controls men with lung and stomach cancer had greater area of raised lesions in aorta and coronary arteries, those with bowel cancer - in coronary arteries. In women with lung cancer area of raised lesions exceeded that of controls only in aorta. Proportion of lung cancer among all tumors was higher in the second compared with the first study (in men 32.7 and 23.2%, in women 10.6 and 4.8%, respectively). Among victims of lung cancer extent of atherosclerosis was greater in smokers compared with nonsmokers.
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PMID:[Atherosclerosis in victims of cancer]. 1249 19

Cigarette smoking as an addictive habit has accompanied human beings for more than 4 centuries. It is also one of the most potent and prevalent environmental health risks human beings are exposed to, and it is responsible for more than 1000 deaths each day in the United States. With recent research progress, it becomes clear that cigarette smoking can cause almost all major diseases prevalent today, such as cancer or heart disease. These detrimental effects are not only present in active smokers who choose the risk, but also to innocent bystanders, as passive smokers, who are exposed to cigarettes not-by-choice. While the cigarette-induced harm to human health is indiscriminate and severe, the degree of damage also varies from individual to individual. This intersubject variability in cigarette-induced pathologies is partly mediated by genetic variants of genes that may participate in detoxification process, eg, cytochrome P450 (CYP), cellular susceptibility to toxins, such as p53, or disease development. Through population studies, we have learned that certain CYP1A1 variants, such as Mspl polymorphism, may render the carriers more susceptible to cigarette-induced lung cancer or severe coronary atherosclerosis. The endothelial nitric oxide synthase intron 4 rare allele homozygotes are more likely to have myocardial infarction if they also smoke. In vitro experimental approach has further demonstrated that cigarettes may specifically regulate these genes in genotype-dependent fashion. While we still know little about genetic basis and molecular pathways for cigarette-induced pathological changes, understanding these mechanisms will be of great value in designing strategies to further reduce smoking in targeted populations, and to implement more effective measures in prevention and treatment of cigarette-induced diseases.
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PMID:Genetic influence on cigarette-induced cardiovascular disease. 1270 94

Patients suffering from atherosclerotic diseases are prone to repeated episodes of ischemia/reperfusion that has been demonstrated to induce oxidative stress by formation of oxygen free radicals. It might therefore be expected that such endogenously exposure to free radicals increases the individual cancer risk in patients with atherosclerotic diseases. We therefore studied the sex-specific risk of lung cancer and other cancers in atherosclerotic patients in a prospective study conducted in the Copenhagen area. The study cohort was linked to the Danish Hospital Discharge Register and we identified 2261 1-year survivors of atherosclerotic diseases through 1977 and 1993, while 26150 of the study subjects had no record of an atherosclerotic diagnosis. After linkage to the Danish Cancer Registry associations between atherosclerosis and cancer were analysed for each sex separately by means of Cox proportional hazard regression models. Atherosclerotic women had a significant RR of lung cancer of 3.26 (95% CI: 1.95-5.46) compared to non-atherosclerotic women after adjustment for age, calendar period, study population, smoking habits, school education and alcohol consumption. No significant risk of male lung cancer, RR=1.12 (95% CI: 0.77-1.64), or other smoking-related cancers in either sex was observed after multivariate adjustment. Atherosclerosis did not predict non-smoking-related cancers in general in either men, RR=0.91 (95% CI 0.69-1.20), or women, RR=0.93 (95% CI: 0.64-1.35). We hypothesize that oxidative stress due to episodes of ischemia/reperfusion increases the risk of lung cancer in atherosclerotic females because of a gender specific susceptibility to oxidative DNA damage.
Lung Cancer 2003 Dec
PMID:Association between atherosclerosis and female lung cancer--a Danish cohort study. 1464 11

Cigarette smoke is a major risk factor for human diseases, such as lung cancer and atherosclerosis. The present study was undertaken to investigate the effect of non-fractionated water-soluble cigarette smoke extract (NFWS CSE) on DNA damage and cellular adhesion molecule expression in human umbilical vein endothelial cells (HUVECs). DNA damage and the surface expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by the use of the comet assay and flow cytometry, respectively. NFWS CSE-induced DNA damage in a dose-dependent manner during a 2 h exposure. Pretreatment with ascorbic acid or alpha-tocopherol completely inhibited the NFWS CSE-induced DNA damage. NFWS CSE exposure also up-regulated the surface expression of ICAM-1 and E-selectin in HUVECs. Pretreatment with ascorbic acid or alpha-tocopherol had no effect on NFWS CSE-induced E-selectin and ICAM-1 expression. In contrast, the non-antioxidant metal chelator 1,10-phenanthroline partially suppressed the surface expression of ICAM-1 and E-selectin. These results suggest that NFWS CSE exposure induces both DNA damage and the surface expression of adhesion molecules in HUVECs. However, the molecular mechanism of these effects may be through different pathways: reactive oxygen species are involved in NFWS CSE-induced DNA damage but have little relation to NFWS CSE-induced E-selectin and ICAM-1 expression.
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PMID:Extracts from cigarette smoke induce DNA damage and cell adhesion molecule expression through different pathways. 1556 Aug 90

Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer. In the present study, we have synthesized an analog of curcumin and biomonitored its influence over biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats. The effects were compared with that of curcumin, a well-known antioxidant and anti-hyperlipidemic agent. Toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks), and curcumin (80 mg/kg) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Measurements of activities of the biochemical marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase and of plasma lipid profiles were used to monitor the anti-hyperlipidemic effects of curcuminoids. In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed. Administration of curcumin or curcumin analog to nicotine-treated rats significantly reduced the activity of marker enzymes and plasma lipid levels. Thus, our findings suggest that curcumin and its analog exert an anti-hyperlipidemic effect against nicotine-induced lung toxicity and may be a promising agent for treatment of hyperlipidemia and atherosclerosis.
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PMID:Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats. 1611 19

Epidemiological, clinical, and experimental evidence correlates current levels of ambient air pollution with both respiratory and cardiovascular effects. Oxidative stress, inflammation, induction of a pro-coagulatory state and dysfunction of the autonomic nervous system appear to play a major role. Acute effects include changes in lung function, heart rate, blood pressure and inflammatory state, and clinical measures such as respiratory symptoms, thrombosis, myocardial infarction, arrhythmia, stroke, and death. In addition, there is an increase in the use of health care resources due to these effects. Long-term consequences of cumulated exposure include adverse effects on lung growth, chronic bronchitis, lung cancer, and probably the development of asthma and atherosclerosis. These morbidities ultimately lead to shorter life expectancy. Host factors including genotype are important modifiers of the effects of air pollution. Further research will help identify susceptible subgroups and disentangle specific effects and mechanisms associated with various constituents and sources of air pollution.
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PMID:Air pollution: from lung to heart. 1651 5

Since the London fog of 1952, in which more than 4000 people were killed in 4 days, the combined efforts of scientists from several disciplines, including those from the environmental health, clinical and biomedical disciplines, have raised serious concerns about the impact of air pollutants on human health. These environmental pollutants are rapidly being recognized as important and independent risk factors for several diseases such as asthma, chronic obstructive pulmonary disease, lung cancer, atherosclerosis, ischemic heart disease and stroke. Although the relative effects of particulate matter air pollution (aerodynamic diameter <10 microm, or PM(10)) are greater for respiratory than for cardiovascular deaths, the number of deaths attributable to PM(10) is much larger for cardiovascular than for respiratory reasons due to the higher prevalence of cardiovascular disease in the general population. This review summarizes current understanding of the mechanisms underlying the associations between PM(10) exposure and cardiovascular morbidity and mortality.
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PMID:The pharmacology of particulate matter air pollution-induced cardiovascular dysfunction. 1692 Jan 97

Although the cardiovascular morbidity and mortality induced by cigarette smoking exceed those attributable to lung cancer, the molecular basis of smoking-induced vascular injury remains unclear. To test the link between cigarette smoke, oxidative stress, and vascular inflammation, rats were exposed to the smoke of five cigarettes per day (for 1 wk). Also, isolated arteries were exposed to cigarette smoke extract (CSE; 0 to 40 microg/ml, for 6 h) in organoid culture. We found that smoking impaired acetylcholine-induced relaxations of carotid arteries, which could be improved by the NAD(P)H oxidase inhibitor apocynin. Lucigenin chemiluminescence measurements showed that both smoking and in vitro CSE exposure significantly increased vascular O(2)(*-) production. Dihydroethidine staining showed that increased O(2)(*-) generation was present both in endothelial and smooth muscle cells. CSE also increased vascular H(2)O(2) production (dichlorofluorescein fluorescence). Vascular mRNA expression of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha and that of inducible nitric oxide synthase was significantly increased by both smoking and CSE exposure, which could be prevented by inhibition of NAD(P)H oxidase (diphenyleneiodonium and apocynin) or scavenging of H(2)O(2). In cultured endothelial cells, CSE elicited NF-kappaB activation and increased monocyte adhesiveness, which were prevented by apocynin and catalase. Thus we propose that water-soluble components of cigarette smoke (which are likely to be present in the bloodstream in vivo in smokers) activate the vascular NAD(P)H oxidase. NAD(P)H oxidase-derived H(2)O(2) activates NF-kappaB, leading to proinflammatory alterations in vascular phenotype, which likely promotes development of atherosclerosis, especially if other risk factors are also present.
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PMID:Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. 1707 26

Cardiovascular diseases and cancer (especially lung cancer) are leading causes of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Some have implicated systemic inflammation, which is commonly observed in COPD, as the potential mechanistic bridge between COPD and these disorders. This concept has been supported by animal studies especially in rabbits, which have clearly demonstrated the effect of local lung inflammation on systemic inflammation and on the progression of atherosclerosis and by cross-sectional population-based studies, which have shown a significant relationship between systemic inflammation, as measured by circulating C-reactive protein (CRP) and the risk of cardiovascular diseases in COPD patients. These data have been further extended by a recent study that has elucidated the temporal nature of the relationship between systemic inflammation and the risk of cardiovascular events and cancer in COPD patients. This study showed that baseline CRP levels predicted the incidence of cardiovascular events and cancer-specific mortality over 7 to 8 years of follow-up. CRP levels also predicted all-cause mortality. Collectively, these data indicate that systemic inflammation may play an important role in mediating the extra-pulmonary complications of COPD. Systemic inflammation may contribute substantially to the overall morbidity and mortality of COPD patients.
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PMID:Systemic inflammation and mortality in chronic obstructive pulmonary disease. 1748 53


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