Globular adiponectin but not full-length adiponectin induces increased procoagulability in human endothelial cells.
Adiponectin (APN), a recently discovered adipocytokine, is present in human serum in a full length (fAPN) and a globular form (gAPN). gAPN is a proteolytic cleavage product of fAPN and seems to show independent biological activities compared to the properties of fAPN. The influence of gAPN and fAPN on procoagulability of cells is still unknown. This study examined the effect of gAPN and fAPN on the expression of tissue factor (TF), the initiator of the extrinsic coagulation system, in human umbilical vein endothelial cells (HUVECs). TF activity was measured by a chromogenic assay, TF mRNA by real-time PCR and TF protein by western blot. We found TF activity to be increased after activation by gAPN (3 microg/mL) compared to a non-stimulated control (169.0+/-19.23 U versus 501.9+/-38.95 U, p<0.001). Furthermore, TF mRNA and TF protein was increased dose-dependently after gAPN stimulation. The gAPN-induced rise of TF activity and TF mRNA was significantly reduced by inhibition of the MAP kinases ERK1/2, p38 and JNK. Contrary to gAPN, stimulation with fAPN did not lead to these procoagulant effects. In conclusion, gAPN increased TF transcription, expression and activity in HUVECs. Therefore, our data support the theory that gAPN but not fAPN supports the cellular procoagulability via TF upregulation.
Bobbert
Peter
P
Department of Cardiology and Pneumology, Charité - Universitätsmedizin Medizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12203 Berlin, Germany.
Antoniak
Silvio
S
Schultheiss
Heinz-Peter
HP
Rauch
Ursula
U
D052242:Adiponectin / Q000494:pharmacology*; D000906:Antibodies / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054419:Receptors, Adiponectin / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism
D052242:Adiponectin; D000906:Antibodies; D054419:Receptors, Adiponectin; D013925:Thromboplastin; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3