Increased synthesis of thromboxane A(2) and expression of procoagulant activity by monocytes in response to arachidonic acid in diabetes mellitus.
Thromboxane A(2) (TXA(2)) synthesis and expression of procoagulant activity (PCA) were investigated in mononuclear cells and monocytes prepared from a control and a Type 2 diabetic group. Monocytes from the diabetic group produced 2.10+/-0.81 ng of TXB(2)/5 x 10(5) monocytes compared to 1.26+/-0.43 ng/5 x 10(5) monocytes by the control group (P<0.01, n=11) when incubated in autologous plasma containing arachidonic acid (200 microg/ml). When monocytes were incubated in buffer containing arachidonic acid (20 microg/ml), cells from the diabetic group produced 1.65+/-0.68 ng of TXB(2)/5 x 10(5) monocytes compared to 1.07+/-0.31 ng/5 x 10(5) monocytes by the control group (P<0.02, n=12). Expression of PCA was examined in mononuclear cell preparations. Basal and maximally stimulated PCA with lipopolysaccharide (4.2 microg/ml) were not different between control and diabetic groups. However, arachidonic acid induced a four-fold (P<0.001) increase in PCA in the diabetic group. This activity was characterized as tissue factor. Increased synthesis of TXA(2) and expression of PCA may potentiate thrombosis and increase fibrin deposition, events that play primary roles in the development of vascular disease.
Konieczkowski
M
M
Rammelkamp Center for Research and Education at MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Skrinska
V A
VA
D016718:Arachidonic Acid / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000209:etiology; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology; D005260:Female; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology; D013928:Thromboxane A2 / Q000096:biosynthesis*
D001779:Blood Coagulation Factors; D016895:Culture Media, Serum-Free; D008070:Lipopolysaccharides; C045071:leukocyte procoagulant activity; D016718:Arachidonic Acid; D013928:Thromboxane A2