Association between enhanced soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy.
BACKGROUND
Hypercholesterolemia is associated with inflammation and the prothrombotic state. CD40-CD40 ligand (CD40L) interactions promote a prothrombotic response in nucleated cells. The aim of this study was to characterize the in vivo expression of soluble CD40L (sCD40L) in hypercholesterolemia, to correlate it with the extent of the prothrombotic state, and to investigate whether it may be modified by statins.


RESULTS
We studied 80 hypercholesterolemic patients and 80 matched healthy subjects. Hypercholesterolemic subjects had enhanced levels of sCD40L, factor VIIa (FVIIa), and prothrombin fragment 1+2 (F1+2) compared with healthy subjects. sCD40L correlated with total cholesterol and LDL cholesterol. Moreover, sCD40L was positively associated with in vivo platelet activation, as reflected by plasma P-selectin and urinary 11-dehydro-thromboxane B2, and with procoagulant state, as reflected by FVIIa and F1+2. Inhibition of cholesterol biosynthesis by pravastatin or cerivastatin was associated with comparable, significant reductions in sCD40L, FVIIa, and F1+2.


CONCLUSIONS
This study suggests that sCD40L may represent the molecular link between hypercholesterolemia and the prothrombotic state and demonstrates that statin therapy may significantly reduce sCD40L and the prothrombotic state.
Center of Excellence on Aging, University of Chieti G. D'Annunzio School of Medicine, Chieti, Italy.
Francesco
F
Cipollone
Andrea
A
Mezzetti
Ettore
E
Porreca
Concetta
C
Di Febbo
Michele
M
Nutini
Maria
M
Fazia
Angela
A
Falco
Franco
F
Cuccurullo
Giovanni
G
Davì
D023201:CD40 Ligand / Q000097:blood*; D004311:Double-Blind Method; D015942:Factor VIIa / Q000032:analysis; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000652:urine; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D015539:Platelet Activation; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin / Q000032:analysis*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019007:P-Selectin; D010446:Peptide Fragments; D011498:Protein Precursors; D023201:CD40 Ligand; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D015942:Factor VIIa