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Different Isoforms of Tocopherols Enhance Nitric Oxide Synthase Phosphorylation and Inhibit Human Platelet Aggregation and Lipid Peroxidation: Implications in Therapy with Vitamin E

Department of Medicine, University of Florida and VA Medical Center, Gainesville

Tom Saldeen, MD, PhD

Department of Surgery, University of Uppsala, Uppsala, Sweden

Francesco Romeo, MD

Department of Cardiology, University of Rome "Tor Vergata," Rome, Italy

Jawahar L. Mehta, MD, PhD

Department of Medicine, University of Florida and VA Medical Center, Gainesville

Background: oc-Tocopherol has received much attention in the primary and secondary prevention of coronary artery disease. Absence of other isoforms, such as y- and &-tocopherol, in commercial preparations of vitamin E may account for the inconsistent results of clinical trials. Since platelet aggregation is intimately involved in thrombogenesis, the relative effects of ox-, y-, and 6-tocopherol and their combination were examined on human platelet aggregation, lipid peroxidation, and constitutive nitric oxide synthase (cNOS) activity.

Methods and Results: Human platelets were incubated with the three different isoforms of tocopherol and their combination for 30 minutes, and then ADP-induced platelet aggregation measured. All three isoforms of tocopherol markedly and similarly decreased platelet aggregation in a concentration (120-480,uM)-dependent manner. All three tocopherols also decreased the level of the lipid peroxidation product, malondialdehyde (MDA), and increased NO release (P < 0.05 vs control). These isoforms of tocopherol did not affect cNOS protein expression, but enhanced cNOS phosphorylation in platelets. The combination of three tocopherols in a concentration found in nature was more potent than oc-, y-, or 6-tocopherol alone in this regard.

Conclusion: These observations suggest that all three major isoforms of tocopherol have a similar effect on human platelet aggregation. The three isoforns appear to attenuate platelet aggregation at least in part via a decrease in free radical generation and an increase in platelet cNOS activity. The combination of tocopherols has a synergistic platelet inhibitory effect. Future clinical trials should concentrate on the combination of these three isoforms of tocopherols.

Key Words: human platelets • tocopherols • free radicals • nitric oxide synthase

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 6, No. 2, 155-161 (2001)
DOI: 10.1177/107424840100600207


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