Is soluble CD40 ligand a mediator of angiogenesis in patients with coronary artery disease?
BACKGROUND
In cardiovascular disease, soluble CD40 ligand (sCD40L) has been associated with an adverse prognosis. Angiogenesis has been implicated in the progression of coronary artery disease (CAD) and sCD40L has pro-angiogenic effects in vitro. Angiogenesis itself is regulated by many mediators, such as vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). Ang-1 promotes vascular maturation whilst Ang-2 destabilises the blood vessel and permits vascular growth with VEGF. Hence, selective elevation of VEGF and Ang-2 suggest a state of vascular plasticity and increased angiogenesis. We hypothesised raised plasma levels of VEGF and Ang-2, but not Ang-1, and correlations with raised sCD40L levels and CAD severity/collateralisation in patients with CAD.


METHODS
We recruited 153 patients attending diagnostic angiography for CAD and 47 healthy controls. Patients with previous revascularisation or unequivocally normal angiograms were excluded. The coronary atheroma score (CAS) and coronary stenosis score (CSS), and the presence of collaterals, were assessed by 2 blinded observers. Plasma sCD40L, VEGF, Ang-1 and -2 levels were measured by ELISA.


RESULTS
Plasma levels of sCD40L, VEGF and Ang-2, but not Ang-1, were higher in CAD patients compared to controls. Both plasma VEGF (r=0.526, p<0.001) and Ang-2 (r=0.429, p<0.001) were correlated with sCD40L, but not with CAS, CSS or collateralisation. On stepwise multivariate regression analysis, plasma sCD40L was an independent predictor of plasma VEGF (p=0.002), and Ang-2 (p<0.001) levels.


CONCLUSIONS
These data suggest abnormal indices of angiogenesis in CAD, which may be associated with increased CD40-CD40L interactions in patients with CAD. Plasma sCD40L, VEGF and Ang-2 levels were not correlated to angiographic CAD/collateralisation.
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham. B18 7QH, England, UK.
Hoong Sern
HS
Lim
Muzahir H
MH
Tayebjee
Kiat T
KT
Tan
Jeetesh V
JV
Patel
Robert J
RJ
Macfadyen
Gregory Y H
GY
Lip
D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism*; D012720:Severity of Illness Index; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D023201:CD40 Ligand