Atorvastatin increases ecNOS levels in human platelets of hyperlipidemic subjects.
BACKGROUND
The purpose of this study was to probe the pleiotrophic effects of Atorvastatin on intraplatelet-nitric oxide metabolism.


RESULTS
Hyperlipidemic subjects (n = 19) were treated for 1 month (following a 3-week washout) with either Atorvastatin or placebo in a double-blinded randomized (n = 2, crossover), placebo-controlled study. Changes in the levels of intraplatelet nitric oxide synthase, nitrotyrosine were correlated with cholesterol, LDL-C, HDL-C and triglyceride levels. These studies indicate that with atrovastatin ecNOS levels increased on average by approximately approximately 1.7-fold (paired t-test p = 0.009). Interestingly, levels of nitrotyrosylated platelet proteins, an indication of peroxynitrite damage, decreased as ecNOS levels increased in presence of the drug (paired t-test p = 0.33). Atorvastatin, at 10 mg per day, lowered cholesterol and LDL-C levels in all patients with the average lowering of approximately 21% and approximately 17% respectively. The effect on HDL was not significant whilst triglyceride levels were lowered by an average of approximately 18%.


CONCLUSIONS
This study adds to the volume of evidence that statins have beneficial effects other than lipid lowering. Here, Atorvastatin is shown to significantly elevate intraplatelet ecNOS levels in hyperlipidemic subjects without affecting iNOS expression. The net result of this would be the elevation of NO production which would promote platelet deaggregation and vasodilation.
Tannous
M
M
Cardiology and Atherosclerosis Research Group, School of Physical Sciences, Chemistry and Biochemistry, University of Windsor, Ontario, Canada.
Cheung
R
R
Vignini
A
A
Mutus
B
B
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D001798:Blood Proteins / Q000737:chemistry; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004790:Enzyme Induction; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000494:pharmacology*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014664:Vasodilation
D000924:Anticholesteremic Agents; D001798:Blood Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009566:Nitrates; D011758:Pyrroles; D014280:Triglycerides; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D002784:Cholesterol; D000069059:Atorvastatin; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III