Vitamin E inhibits collagen-induced platelet activation by blunting hydrogen peroxide.
In this study, we investigated whether vitamin E at concentrations achievable in blood after supplementation inhibits platelet function in humans. Gel-filtered platelets were incubated 30 minutes with scalar concentrations (50 to 250 mmol/L) of vitamin E and then stimulated with collagen. Compared with controls, vitamin E inhibited collagen-induced platelet aggregation and thromboxane A2 formation in a dose-dependent manner. Furthermore, vitamin E inhibited, in a dose-dependent manner, Ca(2+) mobilization and formation of inositol 1,4,5-triphosphate. Because it was previously shown that hydrogen peroxide formation mediates arachidonic acid metabolism and phospholipase C activation in collagen-induced platelet activation, we investigated whether vitamin E was able to blunt hydrogen peroxide. In experiments performed in unstimulated platelets supplemented with hydrogen peroxide and in collagen-stimulated platelets, vitamin E was able to blunt hydrogen peroxide. In 6 healthy subjects given vitamin E for 2 weeks (600 mg/d), we found a significant decrease of collagen-induced H(2)O(2) formation, platelet aggregation, and calcium mobilization. This study demonstrated in vitro and ex vivo that vitamin E inhibits collagen-induced platelet activation by blunting hydrogen peroxide formation.
Pignatelli
P
P
Department of Experimental Medicine and Pathology, University of La Sapienza, Rome, Italy.
Pulcinelli
F M
FM
Lenti
L
L
Gazzaniga
P P
PP
Violi
F
F
D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013928:Thromboxane A2 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage*
D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D014810:Vitamin E; D016718:Arachidonic Acid; D013928:Thromboxane A2; D003094:Collagen; D006861:Hydrogen Peroxide; D010738:Type C Phospholipases; D002118:Calcium