Studies on subfractions of fibrinogen : With special emphasis on fibrinogen quantification, viscosity and inflammation
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AbstractFibrinogen in plasma is heterogeneous and includes 3 main fractions with different molecular weight, solubility and clottability. 70% is high molecular weight (HMW)-fibrinogen with intact Aα-chains, 25% is low molecular weight (LMW)-fibrinogen, and 5% is very low molecular weight (LMW`)-fibrinogen which has lost the C-terminal end of one or both α-chains, respectively. During acute-phase conditions such as bacterial infections, trauma and major surgery, fibrinogen levels and the HMW-/LMW-fibrinogen ratio in plasma increase rapidly due to increased synthesis of HMW-fibrinogen. Through cleavage by thrombin, fibrinogen is converted to fibrin in the last step of the coagulation cascade, which constitutes its main physiological function. Fibrinogen is also a major determinant of plasma viscosity. Increased fibrinogen levels and plasma viscosity are both markers of increased risk of developing atherothrombotic disease.
The aims of our thesis were to investigate the effects of an altered HMW-/LMW fibrinogen ratio on 1) the results of commonly used fibrinogen assays, 2) the viscosity of fibrinogen, and 3) the proinflammatory effects on peripheral blood mononuclear cells. We also wanted to 4) determine the effects of moderate red wine consumption on fibrinogen concentration, fibrinogen subfractions and plasma viscosity.
We found that an increased HMW-/LMW fibrinogen ratio resulted in higher fibrinogen levels using a commonly employed clotting rate assay compared to a reference method. The viscosity of the 3 main fibrinogen subfractions did not differ from that of native fibrinogen. A daily glass of red wine significantly reduced plasma viscosity and fibrinogen levels, creating a beneficial profile with regard to atherothrombotic disease. Fibrinogen and fibrin both upregulated mRNA levels and induced synthesis of the proinflammatory cytokines IL-6 and TNF-α in peripheral blood mononuclear cells in a dose dependent manner.
List of papers
|PAPER I Influence of freeze-drying on the clotting properties of fibrinogen in plasma. Torstein Jensen, Sigrun Halvorsen, Hans C. Godal, Ole H. Skjønsberg. Thrombosis Research 2002; 105: 499– 502. The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1016/S0049-3848(02)00057-9|
|PAPER II Discrepancy between fibrinogen concentrations determined by clotting rate and clottability assays during the acute-phase reaction. Torstein Jensen, Sigrun Halvorsen, Hans C. Godal, Per M. Sandset and Ole H. Skjønsberg. Thrombosis Research 2000; 100: 397-403. The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1016/S0049-3848(00)00344-3|
|PAPER III The viscosity of fibrinogen subfractions and of EDTA denatured fibrinogen do not differ from that of native fibrinogen. Torstein Jensen, Sigrun Halvorsen, Hans C. Godal, Per M. Sandset, Ole H. Skjønsberg. Thrombosis Research 2004; 113: 51–56. The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1016/j.thromres.2004.01.010|
|PAPER IV A daily glass of red wine induces a prolonged reduction in plasma viscosity: a randomized controlled trial. Torstein Jensen, Lars J. Retterstøl, Per M. Sandset, Hans C. Godal, Ole H. Skjønsberg. Blood Coagulation and Fibrinolysis 2006; 17: 471–476. The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1097/01.mbc.0000240920.72930.63|
|PAPER V Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from isolated peripheral blood mononuclear cells. Torstein Jensen, Peter Kierulf, Olav Klingenberg, Gunn Brit Joø, Hans C. Godal, Per M. Sandset, Ole H. Skjønsberg. Thrombosis and Haemostasis 2007; 97: 822-829. The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1160/TH07-01-0039|