Simvastatin reduces CD40 expression in an experimental model of early arterialization of saphenous vein graft.
BACKGROUND
Saphenous vein graft (VG) failure occurs more frequently compared with arterial grafts, and graft thrombosis represents the main cause of early occlusion. Because CD40-CD40L pathway CD40 represents a culprit link between local inflammation and coagulation cascade, we investigate the role of CD40 and its soluble ligand (sCD40L) in the immediate in vitro response of VG to arterial pressures, and the potential effects of Simvastatin (Merck Sharp&Dohme, White-house Station, NJ) supplementation.


METHODS
Samples of saphenous vein and of internal mammary artery (IMA) were obtained from sixteen patients without history of statin therapy. Segments underwent pulsatile pressure distension and culture with or without supplementation of Simvastatin. CD40 and sCD40L were assessed in tissue lysate and in culture supernatant, respectively. sCD40L serum concentrations were also measured.


RESULTS
During the course of the experiment, the CD40 expression was significantly lower in IMA samples compared with both distended and not distended VG. Pressure distension up-regulated the production of CD40 in VG segments after 24 and 48 h. Statin supplementation significantly reduced the expression of CD40 in both venous (P < 0.001) and arterial samples (P < 0.001). This effect of Simvastatin was not affected by the treatment with L-NAME, but it was reversed by the addition of mevalonic acid. Mean sCD40L content in culture supernatants increased over time, suggesting that not only platelets but also the vessel wall is a source of CD40 and sCD40L.


CONCLUSIONS
Simvastatin treatment modulates endothelial CD40-sCD40L in both venous and arterial grafts, and therefore may represent a useful tool in the pharmacological prevention of graft failure.
Chello
Massimo
M
Department of Cardiovascular Research, Interdisciplinary Center for Biomedical Research (CIR), University Campus BioMedico of Rome, Rome, Italy. m.chello@unicampus.it
Spadaccio
Cristiano
C
Anselmi
Amedeo
A
Patti
Giuseppe
G
Lusini
Mario
M
Di Sciascio
Germano
G
Covino
Elvio
E
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001794:Blood Pressure; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D019821:Simvastatin / Q000494:pharmacology*; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control; D015854:Up-Regulation
D000924:Anticholesteremic Agents; D019013:CD40 Antigens; D023201:CD40 Ligand; D009569:Nitric Oxide; D019821:Simvastatin