Vitamin C inhibits platelet expression of CD40 ligand.
Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50-100 microM) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O2- were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O2- were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O2- (-70%, P < 0.001) and CD40L (-68%, P < 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression.
Pignatelli
Pasquale
P
Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Divisione IV Clinica Medica, Policlinico Umberto I, Viale del Policlinico, 00185, Rome, Italy.
Sanguigni
Valerio
V
Paola
Sciacca Giordano
SG
Lo Coco
Emanuela
E
Lenti
Luisa
L
Violi
Francesco
F
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D023201:CD40 Ligand / Q000096:biosynthesis*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D000975:Antioxidants; D001095:Arachidonic Acids; D007211:Indoles; C081565:arachidonyltrifluoromethane; D013481:Superoxides; D023201:CD40 Ligand; D003094:Collagen; D011493:Protein Kinase C; D010741:Phospholipases A; D013917:Thrombin; D001205:Ascorbic Acid; C064758:Ro 31-8220