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)

Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is an active substance present in tobacco. We have analyzed the effect of hesperidin, a bioflavonoid on nicotine induced toxicity. Antioxidant status and expression of MMPs (Matrix metalloproteinases) were analyzed to monitor the protective effect of hesperidin against nicotine toxicity. Our result demonstrated that nicotine significantly up regulates the expression of MMPs and depletes the antioxidant status. On treatment with hesperidin we found the down regulation of expression of MMPs and enhancement in antioxidant status. Hence it could be developed as a drug against tobacco related disease in near future.
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PMID:Effect of hesperidin on matrix metalloproteinases and antioxidant status during nicotine-induced toxicity. 1764 89

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide killing nearly 3 million people annually. Even the most optimistic estimates suggest that COPD mortality rates will increase by 50% over the next 15 years. Individuals with COPD are at increased risk of cardiovascular diseases (CVD), lung cancer, osteoporosis and muscle wasting. Smoking is a well-described risk factor for both COPD and CVD, but CVD in patients with COPD is likely to be due to other factors in addition to smoking. Systemic inflammation may be an important common etiological cause between COPD and CVD, being well described in both diseases. This paper reviews the close relationship between COPD and cardiovascular diseases, principally atherosclerosis. The common pathogenetic mechanisms, relation between cardiovascular comorbidities and pulmonary function parameters, the treatment of pulmonary and systemic inflammation, the role medications in the treatment of both disorders, the effect of cardiovascular comorbidities on the prognosis of COPD and prediction of mortality is discussed. The anti-inflammatory effects of inhaled corticosteroids and statins, their effects on cardiovascular endpoints, all-cause mortality, and survival of COPD patients are reviewed as a new perspective to the treatment.
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PMID:[Chronic obstructive pulmonary disease and cardiovascular system]. 1912 87

The influence of tobacco smoke on human health is still an important problem worldwide. Complex inflammatory processes and changes in the immune system are crucial in the pathogenesis of smoking related disorders like chronic obstructive lung disease (COPD), lung cancer, atherosclerosis. The objective of this review is to present the alterations in the immune system in smokers. The main affected system by cigarette smoke (CS) is the respiratory tract. In bronchial epithelium metaplastic and dysplastic changes are accompanied by elevated expression of adhesion molecules and secretion of many cytokines capable of stimulation immune cells influx. In the population of pulmonary macrophages an elevated proportion of cells, changes in expression surface markers with impaired phagocytic and antigen presenting function are observed. Chronic exposure to CS causes increased production of metalloproteinases (MMP) by macrophages and proteolitic enzymes by neutrophils. These enzymes cause destruction of alveolar wall. Increased apoptosis of lung tissue results in augmentation of foreign material which may play a role of autoantigen and which is a target for cytotoxic/suppressor cells. The role of regulatory T (Treg) cells in this process is recently postulated. Smoking cessation is the most effective method of prophylaxis and treatment of diseases related to tobacco smoking. However many immunological changes in smokers are not completely reversible after quitting smoking.
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PMID:Effects of cigarette smoke on the lung and systemic immunity. 1921 30

Besides atherosclerosis and lung cancer, smoking is considered to play a major role in the pathogenesis of autoimmune diseases. It has long been known that there is a connection between rheumatoid factor-positive rheumatoid arthritis and cigarette smoking. Recently, an important gene-environment interaction has been revealed; that is, carrying specific HLA-DRB1 alleles encoding the shared epitope and smoking establish a significant risk for anti-citrullinated protein antibody-positive rheumatoid arthritis. We summarize how smoking-related alteration of the cytokine balance, the increased risk of infections (the possibility of cross-reactivity) and modifications of autoantigens by citrullination may contribute to the development of rheumatoid arthritis.
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PMID:Rheumatoid arthritis and smoking: putting the pieces together. 1967 9

Different designs can be used to analyze the relationships between respiratory mortality and long term exposure to atmospheric pollution: epidemiological studies (cohort, prevalence study) demonstrate the reality of the relationship and toxicological studies explain it. Cohort studies have the advantage of being able to take into account many confounding factors and thus avoid biases (which is not the case with prevalence studies), but require significant human and financial resources. They were first adopted in the US, but are now more often applied in Europe. The results are relatively consistent, as they all show a statistically significant association between an increase in particulate pollution and cardiopulmonary mortality. Mortality from lung cancer is also associated with long term exposition to particles and sometimes to ozone or nitrogen oxides. Cerebrovascular diseases and sudden death of young children have also been associated with particulate pollution. The relationships are more powerful for long term than short term exposure but are also linear and without threshold. In order to explain these effects (today the causality of the relationship is certain) there are many possible factors, particularly regarding particulate exposures: an increase in cardiovascular risk biomarkers (fibrinogen, white blood cells, and platelets), atherosclerosis, chronic inflammation of lung tissues increased by acute exposure, etc. More and more studies address the interaction between gene and environment and even epigenetic phenomena which could be responsible of these effects. Public Health impact could be quantified. The European E&H surveillance program Apheis, for example, estimated that if PM2.5 levels remained below 15 microg/m(3), a 30 year old person could see his life expectancy increased by 1 month to 2 years, depending on the studied city. Finally, mortality is not the only relevant indicator for health effects of air pollution. ISAAC studies address asthma, allergic rhinitis and eczema among children.
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PMID:[Prolonged exposure to atmospheric air pollution and mortality from respiratory causes]. 2003 41

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Patients with COPD are at increased risk of cardiovascular diseases, osteoporosis and lung cancer. Although some of the associations between COPD and atherosclerosis may be the result of common risk factors such as smoking, epidemiological evidence suggest that impaired lung function is a risk factor for increased cardiovascular death, independent of tobacco use. This phenomenon may be related to common genetic predisposition for atherosclerosis and emphysema. Chronic obstructive pulmonary disease, like atherosclerosis, is a disease of systemic inflammation and may hasten the progression of atherosclerosis and contribute to the higher rate of death in COPD. This article reviews close relationship between COPD and cardiovascular diseases, mainly atherosclerosis. The authors also present some preliminary data suggesting a possible influence of statin therapy on the clinical course of COPD.
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PMID:[Chronic obstructive pulmonary disease and cardiovascular diseases]. 2016 16

Chlamydia pneumoniae is a universal pathogen that has been indicated to play a part in the development of asthma, atherosclerosis and lung cancer. The complete eradication of this intracellular bacterium is in practice impossible with the antibiotics that are currently in use and studies on new antichlamydial compounds is challenging because Chlamydia research lacks the tools required for the genetic modification of this bacterium. Betulin is a natural lupane-class triterpene derived from plants with a wide variety of biological activities. This compound group thus has wide medical potentials, and in fact has been shown to be active against intracellular pathogens. For this reason, betulin and its derivatives were selected to be assayed against C. pneumoniae in the present study. Thirty-two betulin derivatives were assayed against C. pneumoniae using an acute infection model in vitro. Five promising compounds with potential lead compound characteristics were identified. Compound 24 (betulin dioxime) gave a minimal inhibitory concentration (MIC) of 1 microM against strain CWL-029 and showed activity in nanomolar concentrations, as 50% inhibition was achieved at 290 nM. The antichlamydial effect of 24 was confirmed with a clinical isolate CV-6, showing a MIC of 2.2 microM. Previous research on betulin and its derivatives has not identified such a remarkable inhibition of Gram-negative bacterial growth. Furthermore, we also demonstrated that this antichlamydial activity was not due to PLA(2) (EC 3.1.1.4) inhibition caused by the betulin derivatives.
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PMID:Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae. 2061 90

Receptor and non-receptor tyrosine kinases are involved in multiple proliferative signalling pathways. Imatinib, one of the first tyrosine kinase inhibitors (TKIs) to be approved, revolutionized the treatment of chronic myelogenous leukaemia, and other TKIs with different spectra of kinase inhibition are used to treat renal cell carcinoma, non-small-cell lung cancer and colon cancer. Studies also support the potential use of TKIs as anti-proliferative agents in non-malignant disorders such as cardiac hypertrophy, and in benign-proliferative disorders including pulmonary hypertension, lung fibrosis, rheumatoid disorders, atherosclerosis, in-stent restenosis and glomerulonephritis. In this Review, we provide an overview of the most recent developments--both experimental as well as clinical--regarding the therapeutic potential of TKIs in non-malignant disorders.
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PMID:Targeting non-malignant disorders with tyrosine kinase inhibitors. 2111 33

Cathepsins K, L, S, and V are cysteine proteases that have been implicated in tissue-destructive diseases such as atherosclerosis, tumor metastasis, and osteoporosis. Among these four cathepsins are the most powerful human collagenases and elastases, and they share 60% sequence homology. Proper quantification of mature, active cathepsins has been confounded by inhibitor and reporter substrate cross-reactivity, but is necessary to develop properly dosed therapeutic applications. Here, we detail a method of multiplex cathepsin zymography to detect and distinguish the activity of mature cathepsins K, L, S, and V by exploiting differences in individual cathepsin substrate preferences, pH effects, and electrophoretic mobility under non-reducing conditions. Specific identification of cathepsins K, L, S, and V in one cell/tissue extract was obtained with cathepsin K (37 kDa), V (35 kDa), S (25 kDa), and L (20 kDa) under non-reducing conditions. Cathepsin K activity disappeared and V remained when incubated at pH 4 instead of 6. Application of this antibody free, species independent, and medium-throughput method was demonstrated with primary human monocyte-derived macrophages and osteoclasts, endothelial cells stimulated with inflammatory cytokines, and normal and cancer lung tissues, which identified elevated cathepsin V in lung cancer.
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PMID:Manipulating substrate and pH in zymography protocols selectively distinguishes cathepsins K, L, S, and V activity in cells and tissues. 2198 19

STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc.
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PMID:Small interfering RNA against transcription factor STAT6 leads to increased cholesterol synthesis in lung cancer cell lines. 2216 73


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