Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty.
BACKGROUND
Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). CD40-CD40L interaction is involved in the pathogenesis of atherosclerosis; however, its role in the pathophysiology of restenosis is still unclear. We tested the hypothesis that soluble CD40L (sCD40L) may be involved in the process of restenosis and that it exerts its effect by triggering a complex group of inflammatory reactions on endothelial and mononuclear cells.


RESULTS
We studied 70 patients who underwent PTCA and who had repeated angiograms at 6-month follow-up. Plasma sCD40L was measured before and 1, 5, 15, and 180 days after PTCA, whereas plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 were measured before and 24 hours after PTCA. Furthermore, the release of adhesion molecules and MCP-1 and the ability to repair an injury in endothelial cells, as well as the generation of O2- in monocytes, were analyzed in vitro after stimulation with serum from patients or healthy control subjects. Restenosis occurred in 18 patients (26%). Restenotic patients had preprocedural sCD40L significantly higher than patients with favorable outcomes (2.13+/-0.3 versus 0.87+/-0.12 ng/mL, P<0.0001). Elevated sCD40L at baseline was significantly correlated with adhesion molecules and MCP-1 generation after PTCA and with lumen loss at 6-month follow-up. Furthermore, high sCD40L was directly associated in vitro with adhesion molecules and MCP-1 generation and impaired migration in endothelial cells and with enhanced O2- generation in monocytes.


CONCLUSIONS
We conclude that increased sCD40L is associated with late restenosis after PTCA. This may provide an important biochemical link between restenosis and aspirin-insensitive platelet activation. These results provide a rationale for studies with new antiplatelet treatments in patients who underwent PTCA.
Cipollone
Francesco
F
Atherosclerosis Prevention Center, University of Chieti G. D'Annunzio School of Medicine, Chieti, Italy. fcipollone@unich.it
Ferri
Claudio
C
Desideri
Giovambattista
G
Paloscia
Leonardo
L
Materazzo
Guido
G
Mascellanti
Marco
M
Fazia
Maria
M
Iezzi
Annalisa
A
Cuccurullo
Chiara
C
Pini
Barbara
B
Bucci
Marco
M
Santucci
Anna
A
Cuccurullo
Franco
F
Mezzetti
Andrea
A
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000097:blood; D023903:Coronary Restenosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D023921:Coronary Stenosis / Q000276:immunology* / Q000628:therapy; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011237:Predictive Value of Tests; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D018932:Chemokine CCL2; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand