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(Circulation. 2003;108:1676.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
From the Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, University of California Davis Medical Center, Sacramento, Calif.
Correspondence to I. Jialal, MD, PhD, Director, Laboratory for Atherosclerosis and Metabolic Research, 4635 2nd Ave, Room 3000, Research Building 1, Sacramento, CA 95817. E-mail ishwarlal.jialal{at}ucdmc.ucdavis.edu
Received June 27, 2003; revision received August 8, 2003; accepted August 14, 2003.
Background In addition to being a risk marker for cardiovascular disease, much recent data suggest that C-reactive protein (CRP) promotes atherogenesis. Decreased endothelial NO and prostacyclin (PGI2) contribute to a proatherogenic and prothrombotic state. We have shown that CRP decreases endothelial NO synthase expression and bioactivity in human aortic endothelial cells (HAECs). PGI2 is a potent vasodilator and inhibitor of platelet aggregation. Hence, the aim of this study was to examine the effect of CRP on PGI2 release from HAECs and human coronary artery endothelial cells (HCAECs).
Methods and Results HAECs and HCAECs were incubated with human CRP (0 to 50 µg/mL for 24 hours). The release of PGF-1
, a stable product of PGI2, was also assayed in the absence and presence of a potent agonist, A23187. CRP significantly decreased PGF-1
release from HAECs under basal (48% decrease, P<0.001; n=5) and stimulated (26% decrease, P<0.01; n=5) conditions. CRP had no effect on PGI2 synthase (PGIS) mass. By increasing both superoxide and inducible NO synthase, CRP resulted in increased nitration of PGIS by peroxynitrite. The increased nitration and decreased activity of PGIS by CRP was reversed with peroxynitrite scavengers.
Conclusions Thus, CRP decreases PGI2 release from HAECs by inactivating PGIS via nitration, additionally contributing to its atherogenicity.
Key Words: nitric oxide atherosclerosis platelets endothelium inflammation
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