(Circulation. 1996;93:1740-1746.)
© 1996 American Heart Association, Inc.
Articles |
Oxidized LDL Decreases L-Arginine Uptake and Nitric Oxide Synthase Protein Expression in Human Platelets
Relevance of the Effect of Oxidized LDL on Platelet Function
From the Departments of Medicine and Pediatrics, College of Medicine, University of Florida, and the VA Medical Center, Gainesville, Fla.
Correspondence to J.L. Mehta, MD, PhD, University of Florida College of Medicine, PO Box 100277 JHMHC, Gainesville, FL 32610-0277.
Background Oxidized LDL (ox-LDL) promotes vasoconstriction and platelet activation. The present study was undertaken to determine the involvement of the L-arginine–nitric oxide (NO) pathway in ox-LDL–mediated platelet activation.
Methods and Results Washed human platelets were
incubated with native LDL or ox-LDL for 1 hour at 37°C followed by
measurement of platelet function and indexes of the
L-arginine–NO pathway. Ox-LDL but not native LDL caused a
concentration-dependent increase in thrombin-induced
platelet aggregation and 14C-serotonin
release. These effects of ox-LDL were inhibited by pretreatment
of platelets with L-arginine, the precursor of NO.
Ox-LDL also caused a concentration-dependent reduction in the
uptake of 3H-L-arginine by platelets. In
addition, NO synthase activity, measured as conversion of
3H-L-arginine to
3H-L-citrulline, decreased on incubation of
platelet cytosol with ox-LDL. Nitrite production was also
reduced by treatment of platelets with ox-LDL. These effects of
ox-LDL on NO synthase activity and nitrite production were
reversed by pretreatment of platelets with L-arginine.
Concurrent with the decrease in NO production, cytosolic cGMP
was inhibited in ox-LDL–treated platelets. The
inhibitory effects of ox-LDL were dependent in part on the
increase of cholesterol in the platelets. Western blot
analysis demonstrated 
50% reduction in the expression of NO
synthase protein in platelets treated with ox-LDL.
Conclusions These observations indicate that the L-arginine–NO pathway is involved in the effects of ox-LDL on platelet function and that ox-LDL stimulates platelet function primarily by diminishing NO synthase expression as well as decreasing the uptake of L-arginine.
Key Words: vasodilation • vasoconstriction • amino acids • platelets • lipoproteins
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