AUTOIMMUNITY · Autoimmunity, inflammation and thrombosis
6РП — Действия „Мария Кюри“
- Период
- 2005-10-28 → 2007-10-27
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Молекулата SAA и влиянието ѝ върху различни ендотелни клетки се анализират, за да се види как се задействат процеси като съсирването на кръвта. Това помага да се разбере защо пациенти с автоимунни заболявания са по-застрашени от сърдечни проблеми и тромбози.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - AUTOIMMUNITY (Autoimmunity, inflammation and thrombosis)
Patients with autoimmune diseases can develop early signs of heart-associated problems ranging from thromboses to among others, myocardial infarctions. Inflammation and the production of proinflammatory molecules play a key role in these processes. Serum amyloid A (SAA) is one such molecule that is generated during the human acute phase response. SAA is known to be both a sensitive and accurate marker of inflammation associated with the risk of cardiovascular disease. It is also known to play a causal role in atherosclerosis. The main objective of this project was to determine the effects of SAA on different human endothelial cells, since these play a major role in athersclerosis. There are distinct differences in the levels of inflammatory markers and adhesion molecules released in response to SAA between human umbilical vein endothelial cells (HUVEC), human coronary artery endothelial cells (HCAEC) and human microvascular endothelial cells (HMVEC), that could account for the greater responses of coronary artery endothelial cells to inflammation and the beginning of atherosclerosis. SAA also elevated the expression and activity levels of tissue factor, which is one of the most important molecules responsible for coagulation, necessary for the formation of thrombi. SAA stimulates the release of prostacyclin, one of the strongest inhibitors of thrombocyte aggregation, in HCAEC, where prostacyclin seems to act as a protective molecule. For the first time, we show that SAA also affects the transcription factor DNA binding of NF-kappaB, the master regulator of inflammatory cytokines, in coronary artery endothelial cells. These differences could be responsible for the development of early cardiovascular diseases, especially in autoimmune patients, who develop chronic inflammatory conditions. Autoantibodies are produced in autoimmune diseases. The highest number of autoantibodies against SAA (anti-SAA) was found in patients with systemic lupus erytematosus, who also had antiphospholipid syndrome and / or antiphospholipid antibodies. Venous and arterial thrombotic patients showed lower values than blood donors. Since SAA has been indicated as a predicting factor for increased death in acute myocardial infarction patients, it would be relevant to search for correlations of anti-SAA with cardiovascular involvement (particularly myocardial infarction) in the future.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by recurrent thrombosis in presence of circulating antiphospholipid antibodies (aPL). aPL activate endothelial cells (ECs) by up-regulating adhesion molecules, IL-6 production and modulating prostaglandin metabolism. Among aPL, anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) have been shown to induce NF-kappaB nuclear translocation leading to a pro-inflammatory endothelial cell phenotype and thereby inducing acute phase proteins, such as serum amyloid A (SAA). SAA is a cytokine, a marker of inflammation and a predictor of cardiovascular disease.SAA has been shown to bind the same receptor used by the anti-inflammatory lipid mediator Lipoxin A4 (LXA4) and elicit opposing pro-inflammatory effects. An association was found between elevated levels of anti-SAA antibodies and aortic stenosis, deep vein thrombosis, and systemic lupus erythematosus. It is largely unclear how SAA may play a role in pro-thrombotic events. The objective of t his proposal is to understand the role of anti-beta2-GPI antibodies and SAA in activating pro-thrombotic inflammatory responses in the endothelium and to determine the inhibitory effects by which LXA4 could counteract these molecular signaling pathways.Our hypothesis states that anti-beta2-GPI antibodies and SAA play relevant roles in the regulation of NF-kappaB, AP-1 and Egr-1. We will use primary ECs and endothelial cell lines to determine the molecular events by which anti-beta2-GPI antibodies and SAA i n presence and absence of LXA4 affect the transcriptional regulation of target genes (such as IL-6, IL-8, tissue factor). We will also determine whether anti-SAA autoantibodies are associated with cardiovascular inflammation in autoimmune diseases. In summary, results from the proposed study have a potential for providing a novel therapeutic approach to treatment of inflammatory events related to cardiovascular manifestations of autoimmune diseases.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY MEDICAL CENTRE LJUBLJANA DEPARTMENT OF RHEUMATOLOGY · LJUBLJANAКоординаторНиво градСловения
Връзки
Данни: CORDIS, © Европейски съюз