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Autoimmunity, inflammation and thrombosis

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.