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

CD1d-restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during an immune response. The identification of alpha-galactosylceramide (alpha-GalCer), a marine sponge-derived glycosphingolipid, as a potent stimulator of NKT cells led many laboratories to investigate the effects of NKT cell activation on the regulation of immune responses. These studies revealed that alpha-GalCer induces rapid and robust cytokine production by NKT cells, secondary activation of a variety of innate and adaptive immune cells, and modulation of Th cell responses. Further, alpha-GalCer influences disease progression in a variety of experimental models of autoimmunity and inflammation in mice, including models for type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and atherosclerosis. While these studies have raised significant enthusiasm for manipulation of NKT cells as a means of preventing autoimmunity in the clinical setting, there are significant concerns regarding the safety of repeated alpha-GalCer injections in human subjects.
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PMID:Natural killer T cells as targets for immunotherapy of autoimmune diseases. 1518 63

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor. To date, three PPARs isoforms have been isolated and termed alpha, beta (or delta), and gamma. Although PPAR gamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrated that PPAR gamma is present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D(2) (PGD(2)) metabolite, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), are well-known as ligands for PPAR gamma. After it has been reported that activation of PPAR gamma suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPAR gamma have grown and a huge research effort has been concentrated. PPAR gamma, is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Moreover, PPAR gamma ligands have potent tumor modulatory effects against colorectal, prostate, and breast cancers. Recent studies suggest that TZDs not only ameliorate insulin sensitivity but also have pleiotropic effects on many tissues and cell types. Although activation of PPAR gamma seems to have beneficial effects on atherosclerosis and heart failure, the mechanisms by which PPAR gamma ligands prevent the development of cardiovascular diseases are not fully understood. This review will focus on the latest developments in the PPAR gamma field and the roles of PPAR gamma-dependent pathway in cardiovascular diseases.
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PMID:Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases. 1532 Jul 43

As our understanding of integrins as multifunctional adhesion and signaling molecules has grown, so has their recognition as potential therapeutic targets in human diseases. Leukocyte integrins are of particular interest in this regard, as they are key molecules in immune-mediated and inflammatory processes and are thus critically involved in diverse clinical disorders, ranging from asthma to atherosclerosis. Antagonists that interfere with integrin-dependent leukocyte trafficking and/or post-trafficking events have shown efficacy in multiple preclinical models, but these have not always predicted success in subsequent clinical trials (e.g., ischemia-reperfusion disorders and transplantation). However, recent successes of integrin antagonists in psoriasis, inflammatory bowel disease, and multiple sclerosis demonstrate the tremendous potential of antiadhesion therapy directed at leukocyte integrins. This article will review the role of the leukocyte integrins in the inflammatory process, approaches to targeting leukocyte integrins and their ligands, and the results of completed clinical trials.
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PMID:Targeting leukocyte integrins in human diseases. 1554 73

Inflammation is now recognized as a key component in a number of diseases such as atherosclerosis, rheumatoid arthritis, and inflammatory bowel disease. The transcription factor NF-kappaB has been shown to be involved in both the early and late stages of the inflammatory-proliferative process. In this report, we describe the identification of the pathway-selective estrogen receptor (ER) ligand, WAY-169916, that inhibits NF-kappaB transcriptional activity but is devoid of conventional estrogenic activity. This pathway-selective ligand does not promote the classic actions of estrogens such as stimulation of uterine proliferation or ER-mediated gene expression, but is a potent antiinflammatory agent, as demonstrated in the HLA-B27 transgenic rat model of inflammatory bowel disease. Our results indicate the potential utility of pathway-selective ER ligands such as WAY-169916 in the treatment of chronic inflammatory diseases.
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PMID:Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activity. 1569 42

The discovery that platelets express CD40 and the CD40 ligand has transformed these cells, once seen as exclusively involved in coagulation and thrombosis, into active players of immunity and inflammatory injury. Many of the broad and potent biological activities mediated through the CD40/CD40 pathway by immune and nonimmune cells are also exerted by activated platelets. This occurs either through the constitutive expression of CD40 on the platelet surface or the activation-induced expression of the CD40 ligand, which is membrane bound and released from the surface in a soluble form. The most prominent activities mediated by the platelet CD40/CD40 ligand pathway include inflammatory, immunoregulatory, and hemostatic functions, all of which contribute to the newly expanded view of platelets as key biological mediators involved in disease processes such as atherosclerosis, inflammatory bowel disease, and diabetes. Therefore, considering platelet CD40 and CD40 ligand as novel biological targets is justified and supported by animal studies. The clinical profit to be gained from blocking this molecular pair will be determined by results in humans with conditions in which the platelet CD40/CD40 ligand pathway is crucially involved in disease pathogenesis.
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PMID:Platelet activation and the CD40/CD40 ligand pathway: mechanisms and implications for human disease. 1595 32

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

Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Arterial and venous system may be involved. Moreover, mesenteric microvascular thrombosis has been hypothesised as a contributing factor in the pathogenesis of IBD. Early atherosclerosis is a clinical feature common to several inflammatory and immunological diseases in which atherothrombotic complication represents one of the most important cause of mortality and morbidity. We investigate the prevalence and the entity of the early stages of vascular disease in a population of IBD patients without the classical cardiovascular risk factors, by measuring the intima-media thickness (IMT) of the common carotid artery. We found that IBD patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid IMT and that homocysteine levels and age were independently associated with the increased arterial wall thickness.
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PMID:Early atherosclerosis in patients with inflammatory bowel disease. 1649 4

Over the last decades, scientific advances in the knowledge of anti-inflammatory properties of lipids have lead to the development of new formulas for enteral and parenteral nutrition. These products have been utilised as a treatment for a variety of inflammatory diseases. In this review we expose the effects of lipids used in enteral nutriton on different inflammatory pathologies such as inflammatory bowel disease, atherosclerosis, lung fibrosis, rheumatoid arthritis, and others. During inflammatory diseases, eicosanoids are produced from polyunsaturated fatty acids present in cellular membranes. Inflammatory activity of these molecules depends on the nature of their precursors: when arachidonic acid (n-6) is present, pro-inflammatory molecules are released, whereas eicosapentaenoic acid (n-3)-derived eicosanoids are weakly inflammatory. In this way, fish oils, rich in n-3 polyunsaturated fatty acids, increase the content of eicosapentaenoic-eicosanoids and decrease arachidonic acid in immune and endothelial cells leading to a lower inflammatory activity. Likewise, oleic acid exhibits anti-inflammatory effects by preventing the release of particular chemotactic molecules. In summary, enteral diets supplemented with n-3 polyunsaturated fatty acids and oleic acid benefits the treatment of patients with inflammatory pathologies, leading to better outcomes, and decreasing the doses of anti-inflammatory drugs, which exhibit important secondary effects.
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PMID:Importance of lipids in the nutritional treatment of inflammatory diseases. 1677 Oct 71

Epidemiological data suggest a link between chronic inflammation condition and atherosclerosis. Infection and inflammation can also impair lipoprotein metabolism and produce a wide variety of changes in plasma concentrations of lipids and lipoproteins. Twenty-one patients with inflammatory bowel diseases (IBDs) and 28 healthy subjects were recruited. Serum concentrations of lipids, lipoproteins, apolipoproteins, leptin, ghrelin, and inflammation markers (C-reactive protein and serum amyloid A) were measured, and subjects' lipoproteins were characterized. The ability of patients with serum IBD to efflux free cell cholesterol was measured. Serum cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A-I, apoC-II, apoC-III bound to apoB, phospholipid, and phospholipids not bound to apoB levels were significantly lower, whereas serum triglyceride, serum amyloid A, and C-reactive protein levels were significantly higher in patients with active IBD. Apolipoprotein A-I immunoreactivity (pre-beta small particles and small alpha-high-density lipoprotein particles) is decreased in patients with IBD. In contrast, apoE immunoreactivity (slow/small apoE containing lipoprotein particles [LpE particle]) increased in these patients. The efflux capacity of serum from patients with IBD using [(3)H]-cholesterol-labeled Fu5AH cells was reduced (P < .005). Our results demonstrate that, in subjects with active IBD, inflammation leads to alterations in lipid, apolipoprotein, and lipoprotein profiles and reduced cholesterol efflux. These changes are similar to those proposed to promote atherogenesis and may contribute to the development of cardiovascular events.
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PMID:Altered lipid, apolipoprotein, and lipoprotein profiles in inflammatory bowel disease: consequences on the cholesterol efflux capacity of serum using Fu5AH cell system. 1678 73


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