Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly inhibit phospholipase D and superoxide anion generation. Activation of LXA4 receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer LX at the ALXR, and identify new templates for antiinflammatory drugs by design.
 ...
PMID:Polyisoprenyl phosphates: natural antiinflammatory lipid signals. 1208 74

This study was undertaken to demonstrate the unique specificity of the chemokine receptor CXCR4 antagonist AMD3100. Calcium flux assays with selected chemokine/cell combinations, affording distinct chemokine receptor specificities, revealed no interaction of AMD3100 with any of the chemokine receptors CXCR1 through CXCR3, or CCR1 through CCR9. In contrast, AMD3100 potently inhibited CXCR4-mediated calcium signaling and chemotaxis in a concentration-dependent manner in different cell types. Also, AMD3100 inhibited stromal cell-derived factor (SDF)-1-induced endocytosis of CXCR4, but did not affect phorbol ester-induced receptor internalization. Importantly, AMD3100 by itself was unable to elicit intracellular calcium fluxes, to induce chemotaxis, or to trigger CXCR4 internalization, indicating that the compound does not act as a CXCR4 agonist. Specific small-molecule CXCR4 antagonists such as AMD3100 may play an important role in the treatment of human immunodeficiency virus infections and many other pathological processes that are dependent on SDF-1/CXCR4 interactions (e.g. rheumatoid arthritis, atherosclerosis, asthma and breast cancer metastasis).
 ...
PMID:Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. 1222 Jun 70

Exercise-induced collapse and sudden death are unusual in childhood. For this reason, a study was undertaken of a series of 12 cases of sudden death in childhood occurring during physical exertion associated with sporting activities. The age range was 7 to 16 years (mean 12.3 years, M:F ratio 5:1). Deaths resulted from trauma associated with the sporting activity, from an idiosyncratic response to exertion, or from exacerbation of a known underlying disease. Trauma was directly fatal (n = 4: vascular trauma in 1, head injury in 2, drowning in 1), exacerbated an underlying medical condition (n = 1: hypertrophic obstructive cardiomyopathy), or followed collapse from underlying organic disease (n = 1: drowning in epilepsy). Deaths after exertion occurred when there was an unexpected response to underlying occult disease (n = 4: aortic stenosis in 1, cerebral arteriovenous malformation in 1, hypertrophic obstructive cardiomyopathy in 1, coronary atherosclerosis in 1) or to preexisting known disease (n = 2: surgically corrected transposition of the great vessels in 1, asthma in 1). The fatal episodes often resulted from a complex interplay of a variety of factors, including physical exertion, possible trauma, and underlying organic disease. Testing of other family members may be indicated in cases where a rare, possibly familial, disease is found. Evaluation of cases required descriptions of activities before death, information from the medical history of the deceased, and detailed findings from the autopsy.
 ...
PMID:Childhood sporting deaths. 1246 14

The ability to cause persistent infection is one of the major characteristics of all chlamydial species in their appropriate hosts. Persistent infection with Chlamydia trachomatis and Chlamydia pneumoniae has been implicated in the pathogenesis of many chronic diseases, some initially not thought to be infectious, including pelvic inflammatory disease, arthritis, asthma, and atherosclerosis. Chlamydiae have a unique developmental cycle with morphologically distinct infectious and reproductive forms: elementary (EB) and reticulate bodies (RB). Chlamydiae appear to circumvent the host endocytic pathway and inhabit a nonacidic vacuole that is dissociated from late endosomes and lysosomes. Chlamydiae also have been demonstrated to enter a persistent state after treatment with cytokines such as interferon-gamma (IFN-gamma), treatment with antibiotics, or restriction of certain nutrients, or to enter this state spontaneously under certain culture conditions. While the organism is in the persistent state, metabolic activity is reduced, and the organism is often refractory to antibiotic treatment. Ultrastructural analysis of IFN-gamma-treated C pneumoniae demonstrates atypical inclusions containing large reticulate-like aberrant bodies with no evidence of redifferentiation into EBs. Persistent C pneumoniae infection appears to be associated with continued expression of genes associated with DNA replication but not with those genes involved with bacterial cell division. The latter observation may explain the appearance of the large abnormal RBs seen in ultrastructural studies. Studies of the association of chlamydiae with chronic disease have been hampered by difficulties in diagnosing chronic, persistent infection with the organism, which, in turn, render determining the efficacy of antibiotic therapy very difficult.
 ...
PMID:The intracellular life of chlamydiae. 1249 Dec 29

The ADAMs are a family of membrane proteins possessing a disintegrin and metalloprotease domain. Currently, 34 members are known to exist. Approximately 50% of the ADAMs contain a metalloprotease-like domain and some of these have been shown to possess protease activity. Most of the protein substrates identified to date for ADAMs are either integral membrane or extracellular matrix (ECM) proteins. In addition to hydrolysing proteins, a number of ADAMs bind to integrins. The attachment to integrins occurs via the disintegrin domain. Since the ADAMs can play a role in both proteolysis and adhesion, they have been implicated in a variety of biological processes such as sperm-egg fusion, somatic cell-cell adhesion, ectodomain shedding, myoblast fusion and development. Altered expression of certain ADAMs has been associated with a number of diseases including asthma, arthritis, Alzheimer's disease, atherosclerosis and cancer.
 ...
PMID:The ADAMs family of proteins: from basic studies to potential clinical applications. 1266 15

The absence or deficiency of specific platelet glycoprotein receptors has a well-defined role in causing several rare bleeding disorders such as Bernard-Soulier syndrome or Glanzmann's thrombasthenia. Several new rare disorders caused by defects in other receptors or their signalling pathways have recently been described. Platelet receptors are also often targets for antibodies in pathological conditions. The roles of platelet receptors or their polymorphism variants in diseases such as cardiovascular disorders have started to be intensively investigated over the last 5 years. Many of these findings still remain controversial. Recent evidence points to a fundamental role for platelets and their receptors in the origins of atherosclerosis. Studies on the role of platelet receptors in diseases such as asthma, diabetes and HIV are still at an early stage.
 ...
PMID:Platelet receptors and their role in diseases. 1270 29

The article describes the clinical, virological and immunological data confirming the etiological role of herpes virus in the initiation of atherosclerosis. 226 patients with atherosclerosis of the predominantly coronary localization were examined; hypertension and stenocardia were found in a part of them, while myocardial infarction was diagnosed in 22% of the patients. The control group consisted of patients with other diseases related with infections (bronchial asthma, rheumatism etc.) as well as of healthy persons. A total of 558 patients were examined and it was established that there is a reliable relation between atherosclerosis and the infection of patients with, mainly, herpes virus. The correlation was of the seasonal nature, it was linked to the specific features of an infection process and it was confirmed by the condition of the cholesterol supply and by immunodeficiency in patients. The infectious nature of atherosclerosis demands further research for the sake of finding proof of the etiological role of viruses and bacteria and for the sake of working out the means of prophylaxis and treatment of atherosclerosis aimed at removing the infectious etiological factor.
 ...
PMID:[Role of viral-herpetic infections in the etiology of atherosclerosis: clinical, virological and immunological evidence]. 1274 52

Chemokines are important mediators of leukocyte recruitment and activation that play critical roles in the pathology of inflammatory diseases such as atherosclerosis, rheumatoid arthritis and asthma. The vaccinia virus (strain Lister) expresses a 35 kDa soluble protein ('35K') that binds and inactivates a wide range of CC chemokines. We generated a recombinant adenovirus encoding soluble 35K (Ad35K). Ad35K-infected cell culture medium, containing recombinant 35K, potently reduced migration of CCR5-transfected 293 cells by 95% in response to the CC-chemokine RANTES, but had no effect on cells transfected with the CX3CR1 fractalkine receptor. Delivery of Ad35K to mice in vivo via tail vein injection resulted in expression of recombinant 35K in plasma and increased serum RANTES and MIP-1alpha levels when quantified by ELISA. However, chemotaxis of both CCR5-transfected cells and primary macrophages was inhibited by more than 90% by plasma from Ad35K-infected animals compared with control plasma from animals injected with AdGFP. Furthermore, 35K delivered by intra-peritoneal injection more than halved biogel-induced inflammatory cell recruitment in peritoneal exudates compared to AdGFP medium. These studies identify broad-spectrum CC-chemokine blockade using in vivo adenoviral-mediated recombinant 35K expression as a promising strategy to reduce local and systemic inflammation.
 ...
PMID:Adenoviral-mediated delivery of a viral chemokine binding protein blocks CC-chemokine activity in vitro and in vivo. 1277 60

Oxidized low-density lipoprotein (oxLDL) has been reported as a major participant in the pathogenesis of atherosclerosis. We hypothesized that oxLDL can also interact with granulocytes during inflammatory airway diseases, such as asthma. To test the chemotactic effect of oxLDL, isolated human peripheral granulocytes were added to the upper chambers of Transwell filters and migration in response to oxLDL was determined. Cu+2-oxidized LDL stimulated neutrophil (23.4 +/- 3.2% for 100 microg/ml oxLDL versus 2.9 +/- 1.1% for buffer, P < 0.05) and eosinophil (19.3 +/- 3.5% versus 0.6 +/- 0.02% for buffer, P < 0.05) chemotaxis in a concentration-dependent manner. The magnitude of chemotaxis was dependent on the degree of LDL oxidation. Granulocyte transmigration across IL-1beta-activated human pulmonary microvascular endothelial cell monolayers was similarly stimulated by oxLDL. OxLDL activated significant degranulation of both neutrophils (100.9 +/- 9.8 versus 49.6 +/- 8.4 ng lactoferrin released/5 x 105 neutrophils for buffer, P < 0.05) and eosinophils (342 +/- 115.4 versus 85.8 +/- 30.4 ng eosinophil-derived neurotoxin/1 x 106 eosinophils for buffer, P < 0.05). Therefore, in vivo influx and oxidation of LDL may be an important mediator for the initiation of bronchial inflammation where granulocytes are recruited to the lung.
 ...
PMID:Oxidized low-density lipoprotein activates migration and degranulation of human granulocytes. 1277 45

Selectins are carbohydrate-binding molecules that bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. Further improvements in the efficiency, availability, specificity and pharmacokinetics of selectin inhibitors, and specialized application routes and schedules, hold promise for therapeutic indications.
 ...
PMID:The role of selectins in inflammation and disease. 1282 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>