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)

Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and chloride ions by the heme enzyme myeloperoxidase (MPO) released from activated leukocytes. In addition to its potent antibacterial effects, excessive HOCl production can lead to host tissue damage, with this implicated in human diseases such as atherosclerosis, cystic fibrosis, and arthritis. HOCl reacts rapidly with biological materials, with proteins being major targets. Chlorinated amines (chloramines) formed from Lys and His side chains and alpha-amino groups on proteins are major products of these reactions; these materials are however also oxidants and can undergo further reactions. In this study, the kinetics of reaction of His side-chain chloramines with other protein components have been investigated by UV/visible spectroscopy and stopped flow methods at pH 7.4 and 22 degrees C, using the chloramines of the model compound 4-imidazoleacetic acid and N-alpha-acetyl-histidine. The second-order rate constants decrease in a similar order (Cys > Met > disulfide bonds > Trp approximately alpha-amino > Lys >> Tyr > backbone amides > Arg) to the corresponding reactions of HOCl, but are typically 5-25 times slower. These rate constants are consistent with His side-chain chloramines being important secondary oxidants in HOCl-mediated damage. These studies suggest that formation and subsequent reactions of His side-chain chloramines may be responsible for the targeted secondary modification of selected protein residues by HOCl that has previously been observed experimentally and highlight the importance of chloramine structure on their subsequent reactivity.
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PMID:Kinetic analysis of the role of histidine chloramines in hypochlorous acid mediated protein oxidation. 1588 77

Platelets are an important, albeit generally underappreciated, component of the inflammatory cascade. Platelets are known to contribute to inflammation in atherosclerosis, stroke, and asthma. They produce a large number of proinflammatory lipid mediators and cytokines, and play a vital role in recruitment of leukocytes into inflamed tissue. We review the role of platelets in inflammation, how they assist in the recruitment of leukocytes into lung tissue in asthma, and evidence of their dysfunction in cystic fibrosis (CF). Platelet dysfunction in CF could contribute to pulmonary inflammation and tissue destruction. We hypothesize that platelet activation is important in CF lung disease and suggest research avenues that might help elucidate the role of activated platelets in CF.
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PMID:The inflammatory role of platelets in cystic fibrosis. 1633 20

From the World Congress on Inflammation, held August 20-24, 2005 in Melbourne, Australia, new targets and new drugs for inflammation of the respiratory system (asthma, allergic rhinitis, chronic obstructive pulmonary disease and cystic fibrosis), inflammatory bowel disease (ulcerative colitis and Crohn's disease), arthritis (rheumatoid and osteoarthritis), atherosclerosis and cancer are discussed.
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PMID:Inflammation, the key to much pathology. 1647 28

From the World Congress on Inflammation, held August 20-24, 2005 in Melbourne, Australia, new targets and new drugs for inflammation of the respiratory system (asthma, allergic rhinitis, chronic obstructive pulmonary disease and cystic fibrosis), inflammatory bowel disease (ulcerative colitis and Crohn's disease), arthritis (rheumatoid and osteoarthritis), atherosclerosis and cancer are discussed.
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PMID:Inflammation, the key to much pathology. Highlights from the 7th World Congress on Inflammation, held August 20-24, 2005, in Melbourne, Australia. 1639 24

Various reviews have highlighted the potential immuno-modulating properties of macrolides. Recent data in this field raise the possibility of new therapeutic prospects in cancer and inflammatory diseases (cystic fibrosis, asthma, atherosclerosis, etc.). Advances have also been made in our understanding of the interactions between macrolides and host immune effectors, particularly phagocytes. The third millennium should see exciting new uses of macrolides.
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PMID:Immunological effects of macrolides. 1703 43

Cysteinyl leukotrienes (Cys-LTs) are potent proinflammatory mediators derived from arachidonic acid through the 5-lypoxigenase (5-LO) pathway. They exert important pharmacological effects by interaction with at least two different receptors: Cys-LT(1) and Cys-LT(2). By competitive binding to the Cys-LT(1) receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast, and pranlukast, block the effects of Cys-LTs and alleviate the symptoms of many chronic diseases, especially bronchial asthma and allergic rhinitis. Evidence obtained by randomized clinical trials as also by direct experience derived from patients suffering from asthma and allergic rhinitis justifies a broader role for leukotrienes receptor antagonists (LTRAs). Recently published studies and case reports have demonstrated beneficial effects of LTRAs on other diseases commonly associated with asthma (exercise induced asthma, rhinitis, chronic obstructive pulmonary disease, interstitial lung disease, chronic urticaria, atopic dermatitis, allergic fungal disease, nasal polyposis, and paranasal sinus disease) as well as other diseases not connected to asthma (migraine, respiratory syncytial virus postbronchiolitis, systemic mastocytosis, cystic fibrosis, pancreatitis, vulvovaginal candidiasis, cancer, atherosclerosis, eosinophils cystitis, otitis media, capsular contracture, and eosinophilic gastrointestinal disorders). The aim of this review is to show the most recent applications and effectiveness in clinical practice of the LTRAs.
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PMID:Antileukotriene drugs: clinical application, effectiveness and safety. 1769 39

In the past ten years since the discovery and cloning of members of the P2 receptor family, rapid progress has been made in the field regarding the function and pharmacology of different P2 receptor subtypes. This research resulted in identifying these receptors as important players in the pathology of atherosclerosis, cystic fibrosis, neurodegenerative and autoimmune diseases, among other disorders. The signalling mechanisms whereby P2 receptors mediate pathogenesis are not clear in most cases. Future studies in this field will focus on the integration of signalling pathways coupled to P2 receptors and the generation of specific agonists/antagonists for each receptor subtype to provide strategies for the treatment of a variety of diseases.
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PMID:P2 receptors in health and disease. 1847 31

In addition to their established role in hemostasis, recent studies have identified platelets as key regulators of inflammatory reactions. Upon activation, platelets interact with both endothelial cells and circulating leukocytes. By receptor-mediated activation of interacting cell types and by release of mitogenic, pro-inflammatory and -coagulatory mediators, platelets contribute crucially to the initiation and propagation of pathological conditions and processes such as inflammatory bowel disease or atherosclerosis. In inflammatory lung disease, platelets play a critical role in the recruitment of neutrophils, eosinophils and lymphocytes as shown in experimental models of acute lung injury and allergic airway inflammation. Circulating platelet-leukocyte aggregates have been detected in patients with allergic asthma and cystic fibrosis, and in experimental lung injury. Here, we discuss the molecular mechanisms regulating the interaction of platelets with leukocytes, endothelial cells, and the subendothelial matrix with special regard to platelet kinetics in pulmonary microvessels and the putative role of platelets in inflammatory lung disorders. In light of the existing data from experimental and clinical studies it is conceivable that platelet adhesion molecules and platelet mediators provide promising targets for novel therapeutic strategies in inflammatory lung diseases.
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PMID:Endothelium-platelet interactions in inflammatory lung disease. 1862 43

Several S100 Ca(2+)-binding proteins undergo various post-translational modifications that may alter their intracellular and extracellular functions. S100A8 and S100A9, two members of this family, are particularly susceptible to oxidative modification. These proteins, abundantly expressed in neutrophils and activated macrophages, are associated with acute and chronic inflammatory conditions, including microbial infections, cystic fibrosis, rheumatoid arthritis, and atherosclerosis. They have diverse intracellular roles including NADPH oxidase activation and arachidonic acid transport and can be secreted via a Golgi-independent pathway to exert extracellular functions. Many pro-inflammatory functions have been described for S100A8 and S100A9, but they are also implicated in anti-inflammatory roles in wound-healing and protection against excessive oxidative tissue damage,the latter as a result of their exquisite capacity to scavenge oxidants. Similarly, their genes are induced by proinflammatory (LPS and TNF-alpha) stimuli, but induction is IL-10-dependent, and anti-inflammatory glucocorticoids induce or amplify expression. S100A8 and S100A9 were described recently as damage-associated molecular pattern molecules, which provide a novel, conceptual framework for understanding their functions. However, because of this designation, recent reviews focus solely on their pro-inflammatory functions. Here, we summarize the mounting evidence from functional and gene regulation studies that these proteins may also play protective roles. This review offers an explanation for the disparate, functional roles of S100A8 and S100A9 based on emerging data that post-translational, oxidative modifications may act as a regulatory switch.
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PMID:Oxidative modifications of S100 proteins: functional regulation by redox. 1923 40

Efficient phagocytosis of cells undergoing apoptosis by macrophages is important to prevent immunological responses and development of chronic inflammatory disorders such as systemic lupus erythematosus, cystic fibrosis and atherosclerosis. To study phagocytosis of apoptotic cells (AC) by macrophages in tissue, we validated different apoptosis markers (DNA fragmentation, caspase-3 activation and cleavage of its substrate poly(ADP-ribose)polymerase-1) in combination with macrophage immunostaining. Human tonsils were used as a model because they show a high apoptosis frequency under physiological conditions as well as efficient phagocytosis of AC by macrophages. On the other hand, advanced human atherosclerotic plaques were examined since plaques show severely impaired phagocytosis of AC. Our results demonstrate that the presence of non-phagocytized terminal deoxynucleotidyl transferase end labelling (TUNEL)-positive AC represents a suitable marker of poor phagocytosis by macrophages in situ. Other markers for apoptosis, such as cleavage of caspase-3 or PARP-1, should not be used to assess phagocytosis efficiency, because activation of the caspase cascade and cleavage of their substrates can occur in AC when they have not yet been phagocytized by macrophages.
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PMID:Comparison of apoptosis detection markers combined with macrophage immunostaining to study phagocytosis of apoptotic cells in situ. 1969 Jun 49


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