6 results on '"Otterdal, Kari"'
Search Results
2. Dickkopf-1 enhances inflammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis.
- Author
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Ueland T, Otterdal K, Lekva T, Halvorsen B, Gabrielsen A, Sandberg WJ, Paulsson-Berne G, Pedersen TM, Folkersen L, Gullestad L, Oie E, Hansson GK, and Aukrust P
- Subjects
- Animals, Atherosclerosis pathology, Blood Platelets pathology, Blotting, Western, Carotid Arteries metabolism, Carotid Arteries pathology, Cells, Cultured, Coronary Vessels metabolism, Coronary Vessels pathology, Disease Models, Animal, Endothelium, Vascular pathology, Humans, Mice, Mice, Inbred C57BL, Prognosis, Atherosclerosis metabolism, Blood Platelets metabolism, Endothelium, Vascular metabolism, Gene Expression Regulation, Intercellular Signaling Peptides and Proteins biosynthesis
- Abstract
Objective: Based on the emerging importance of the wingless (Wnt) pathways in inflammation and vascular biology, we hypothesized a role for Dickkopf-1 (DKK-1), a major modulator of Wnt signaling, in atherogenesis and plaque destabilization., Methods and Results: We report increased levels of DKK-1 in experimental (ApoE(-/-) mice) and clinical (patients with coronary artery disease [n=80] and patients with carotid plaque [n=47]) atherosclerosis, both systemically (serum) and within the lesion, with particularly high levels in advanced and unstable disease. We identified platelets as an important cellular source of DKK-1 as shown by in vitro experiments and by immunostaining of thrombus material obtained at the site of plaque rupture in patients with acute ST-elevation myocardial infarction, with strong immunoreactivity in platelet aggregates. Our in vitro experiments identified a role for platelet- and endothelial-derived DKK-1 in platelet-dependent endothelial activation, promoting enhanced release of inflammatory cytokines. These inflammatory effects of DKK-1 involved inhibition of the Wnt/beta-catenin pathway and activation of nuclear factor kappaB., Conclusions: Our findings identify DKK-1 as a novel mediator in platelet-mediated endothelial cell activation. The demonstration of enhanced DKK-1 expression within advanced carotid plaques may suggest that this DKK-1-driven inflammatory loop could be operating within the atherosclerotic lesion.
- Published
- 2009
- Full Text
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3. Chemokines and cardiovascular risk.
- Author
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Aukrust P, Halvorsen B, Yndestad A, Ueland T, Øie E, Otterdal K, Gullestad L, and Damås JK
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- Animals, Atherosclerosis complications, Biomarkers metabolism, Cardiovascular Diseases immunology, Chemokine CCL5 metabolism, Chemokines blood, Chemokines genetics, Coronary Artery Disease etiology, Coronary Artery Disease immunology, Coronary Restenosis etiology, Coronary Restenosis immunology, Disease Progression, Genetic Variation, Heart Transplantation adverse effects, Humans, Inflammation complications, Inflammation Mediators metabolism, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Atherosclerosis immunology, Cardiovascular Diseases etiology, Chemokines metabolism, Inflammation immunology
- Abstract
Based on the importance of inflammation in atherogenesis, recent work has focused on whether plasma markers of inflammation can noninvasively diagnose and prognosticate atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherosclerosis, potentially representing attractive therapeutic targets in atherosclerotic disorders, this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect upstream inflammatory activity, stable levels in individuals, and high stability of the actual protein (eg, long half-life and negligible circadian variation) are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (eg, interleukin- 8/CXCL8 and monocyte chemoattractant protein-1/CCL2) have shown to be predictive for future cardiac events in some studies, their role as clinical biomarkers is unclear, and their ability to predict subclinical atherosclerosis has been disappointing. Further prospective studies, including a larger number of patients, are needed to make any firm conclusion. Based on the participation of several chemokines in atherogenesis, it is possible that in the future, combined measurements of multiple chemokines could reveal as a "signature of disease" that can serve as a highly accurate method to assess for the presence of atherosclerotic disease.
- Published
- 2008
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4. A potential role of the CXC chemokine GROalpha in atherosclerosis and plaque destabilization: downregulatory effects of statins.
- Author
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Breland UM, Halvorsen B, Hol J, Øie E, Paulsson-Berne G, Yndestad A, Smith C, Otterdal K, Hedin U, Waehre T, Sandberg WJ, Frøland SS, Haraldsen G, Gullestad L, Damås JK, Hansson GK, and Aukrust P
- Subjects
- Angina, Unstable metabolism, Angina, Unstable pathology, Aorta metabolism, Aorta pathology, Carotid Stenosis pathology, Case-Control Studies, Cells, Cultured, Chemokine CXCL1 genetics, Coronary Artery Disease pathology, Down-Regulation, Endothelium, Vascular metabolism, Endothelium, Vascular pathology, Enzyme Inhibitors pharmacology, Female, Humans, Leukocytes, Mononuclear metabolism, Leukocytes, Mononuclear pathology, Macrophages metabolism, Macrophages pathology, Male, Matrix Metalloproteinase 1 metabolism, Matrix Metalloproteinase 3 metabolism, Middle Aged, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular pathology, Umbilical Veins metabolism, Umbilical Veins pathology, Carotid Stenosis metabolism, Chemokine CXCL1 metabolism, Coronary Artery Disease metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
- Abstract
Objective: We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in human atherosclerosis., Methods and Results: GROalpha levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GROalpha was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GROalpha was among the 10 most differentially expressed transcripts comparing peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) and healthy controls. (2) Both patients with stable (n=41) and particularly those with unstable (n=47) angina had increased plasma levels of GROalpha comparing controls (n=20). (3) We found increased expression of GROalpha within symptomatic carotid plaques, located to macrophages and endothelial cells. (4) GROalpha enhanced the release of matrix metalloproteinases in vascular smooth muscle cells, and increased the binding of acetylated LDL in macrophages. (5) Atorvastatin downregulated GROalpha levels as shown both in vitro in endothelial cells and macrophages and in vivo in PBMCs from CAD patients. (6) The effect on GROalpha in endothelial cells involved increased storage and reduced secretion of GROalpha., Conclusions: GROalpha could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion.
- Published
- 2008
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5. Soluble CD40 ligand in pulmonary arterial hypertension: possible pathogenic role of the interaction between platelets and endothelial cells.
- Author
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Damås JK, Otterdal K, Yndestad A, Aass H, Solum NO, Frøland SS, Simonsen S, Aukrust P, and Andreassen AK
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- Aged, Anticoagulants therapeutic use, Blood Platelets drug effects, CD40 Ligand genetics, CD40 Ligand pharmacology, Cells, Cultured drug effects, Cells, Cultured metabolism, Chemokine CCL2 biosynthesis, Chemokine CCL2 blood, Chemokine CCL2 genetics, Collagen Diseases complications, Epoprostenol pharmacology, Female, Femoral Artery, Gene Expression Regulation drug effects, HIV Infections complications, Heart Defects, Congenital complications, Humans, Hypertension, Pulmonary etiology, Interleukin-8 biosynthesis, Interleukin-8 blood, Interleukin-8 genetics, Liver Cirrhosis complications, Male, Middle Aged, Peptide Fragments pharmacology, Pulmonary Artery, Recombinant Proteins pharmacology, Solubility, Thromboembolism complications, Umbilical Veins, Warfarin therapeutic use, Blood Platelets physiology, CD40 Ligand physiology, Endothelial Cells physiology, Endothelium, Vascular physiopathology, Hypertension, Pulmonary physiopathology
- Abstract
Background: Inflammatory processes seem to be involved in pulmonary arterial hypertension (PAH). CD40 ligand (L) may promote inflammation and thrombus formation, and we hypothesized that CD40L could be involved in the pathogenesis of PAH., Methods and Results: Several significant findings were revealed when examining the possible role of CD40L in PAH. (1) Patients with primary (n=13) and secondary (n=11) PAH but not those with chronic thromboembolic pulmonary hypertension (n=8) had increased plasma levels of soluble (s) CD40L compared with control subjects (n=8). (2) PAH patients using warfarin had markedly lower sCD40L levels than those without such therapy. (3) sCD40L levels were higher in arterial (femoral artery) compared with mixed venous blood (pulmonary artery), suggesting enhanced release or reduced clearance in the pulmonary vasculature. (4) Platelets from PAH patients showed enhanced spontaneous and SFLLRN-stimulated release of sCD40L compared with control subjects. (5) In vitro, recombinant sCD40L induced monocyte chemoattractant protein (MCP)-1 and interleukin-8 gene expression in endothelial cells, and plasma levels of these chemokines were raised in all PAH groups, significantly correlated to sCD40L and hemodynamic parameters. (6) Although prostacyclin therapy (3 months) showed clinical benefit, this therapy had no effect on sCD40L and increased MCP-1 levels in PAH patients, and prostacyclin enhanced MCP-1 in CD40L-stimulated endothelial cells., Conclusions: Our findings suggest a role for CD40L in the pathogenesis of PAH, possibly operating through an interaction between platelets and endothelial cells involving chemokine-related mechanisms.
- Published
- 2004
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6. Interleukin-7-mediated inflammation in unstable angina: possible role of chemokines and platelets.
- Author
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Damås JK, Waehre T, Yndestad A, Otterdal K, Hognestad A, Solum NO, Gullestad L, Frøland SS, and Aukrust P
- Subjects
- Angina, Unstable blood, Angina, Unstable complications, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Aspirin pharmacology, Blood Platelets drug effects, Cells, Cultured, Chemokine CCL3, Chemokine CCL4, Dose-Response Relationship, Drug, Female, Humans, Inflammation blood, Inflammation complications, Interleukin-7 blood, Interleukin-7 pharmacology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Macrophage Inflammatory Proteins pharmacology, Male, Middle Aged, Monocytes drug effects, Monocytes metabolism, Peptide Fragments pharmacology, RNA, Messenger metabolism, Receptors, Chemokine drug effects, Receptors, Chemokine genetics, Receptors, Chemokine metabolism, Reference Values, Angina, Unstable metabolism, Blood Platelets metabolism, Chemokines metabolism, Inflammation metabolism, Interleukin-7 metabolism
- Abstract
Background: Atherogenesis and plaque destabilization involve immune-mediated mechanisms, but the actual mediators have not been fully clarified. Interleukin (IL)-7 is a regulator of T-cell homeostasis but also may be involved in inflammation. We hypothesized that IL-7 could be involved in the inflammatory processes observed in atherosclerosis and acute coronary syndromes., Methods and Results: To study the role of IL-7 in coronary artery disease, we analyzed IL-7 levels and the effect of this cytokine on inflammatory mediators in patients with stable and unstable angina and in healthy control subjects. Our major findings were (1) Plasma levels of IL-7 were significantly increased in patients with stable (n=30) and unstable angina (n=30) comparing healthy control subjects (n=20), particularly in those with unstable disease. (2) Increased release from activated platelets appeared to be a major contributor to the raised IL-7 levels in patients with angina. (3) IL-7 enhanced the expression of several inflammatory chemokines in peripheral blood mononuclear cells from both healthy control subjects and patients with angina, particularly in those with unstable disease. Similar effects were seen in monocytes but not in T cells. (4) MIP-1alpha further increased the release of IL-7 from platelets in a dose-dependent manner. (5) Aspirin reduced both the spontaneous and the SFLLRN-stimulated release of IL-7 from platelets, and when administered to healthy control subjects for 7 days (160 mg qd), it reduced plasma levels of IL-7., Conclusions: Our findings suggest a role for IL-7-driven inflammation in atherogenesis and the promotion of clinical instability in coronary artery disease involving interactions between platelets, monocytes, and chemokines.
- Published
- 2003
- Full Text
- View/download PDF
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