Relationship of soluble CD40 ligand to vascular endothelial growth factor, angiopoietins, and tissue factor in atrial fibrillation: a link among platelet activation, angiogenesis, and thrombosis?
BACKGROUND
The precise pathophysiologic processes underlying the prothrombotic or hypercoagulable state in patients with atrial fibrillation (AF) remain uncertain. We hypothesized a relationship among abnormal platelet activation, angiogenic factors, and coagulation, thereby contributing to increased thrombogenecity.


METHODS
Plasma levels of soluble CD40 ligand (sCD40L [an index of platelet activation]) and tissue factor (TF [an index of coagulation]), as well as the angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1, and Ang-2, were measured by enzyme-linked immunosorbent assay in 59 patients with chronic AF. Data were compared to 40 age-matched and sex-matched healthy control subjects who were in sinus rhythm.


RESULTS
AF patients had significantly higher levels of sCD40L (p = 0.038), VEGF (p = 0.023), and Ang-2 (p < 0.001), but not Ang-1 (p = 0.363), compared to control subjects. In non-anticoagulated AF patients (n = 28), TF levels were also higher (p = 0.043), in addition to high sCD40L, VEGF, and Ang-2, compared to control subjects. Among AF patients, sCD40L levels correlated strongly with levels of VEGF (r = 0.919; p < 0.001) and Ang-2 (r = 0.546; p = 0.002). VEGF levels were significantly correlated with levels of Ang-2 (r = 0.490; p < 0.001) and TF (r = 0.298; p = 0.044). In multivariate regression analysis, sCD40L levels were independently associated with levels of VEGF (p = 0.003) and Ang-2 (p = 0.005).


CONCLUSIONS
Plasma levels of sCD40L are elevated in patients with AF, and are related to levels of VEGF, Ang-2, and TF. This interaction among platelets, angiogenic markers, and TF may play a role in the generation of the prothrombotic state associated with AF.
Choudhury
Anirban
A
City Hospital, Haemostasis, Thrombosis and Vascular Biology Unit, Dudley Rd, Birmingham B18 7QH, UK.
Freestone
Bethan
B
Patel
Jeetesh
J
Lip
Gregory Y H
GY
D000368:Aged; D042682:Angiopoietins / Q000097:blood*; D001281:Atrial Fibrillation / Q000097:blood* / Q000503:physiopathology; D023201:CD40 Ligand / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood* / Q000503:physiopathology; D015539:Platelet Activation; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D042682:Angiopoietins; D042461:Vascular Endothelial Growth Factor A; D023201:CD40 Ligand; D013925:Thromboplastin