Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:52-57
Published online before print October 31, 2002, doi: 10.1161/01.ATV.0000044461.01844.C9
Published online before print October 31, 2002, doi: 10.1161/01.ATV.0000044461.01844.C9
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© 2003 American Heart Association, Inc.
Vascular Biology |
Peroxisome Proliferator-Activated Receptor 
Ligands Increase Release of Nitric Oxide From Endothelial Cells
From the Department of Medicine, Veterans Affairs and Emory University, Medical Centers, Decatur, Ga.
Correspondence to David S. Calnek, PhD, Atlanta VA Medical Center (151P), 1670 Clairmont Rd, Decatur, GA 30033. E-mail dcalnek{at}hotmail.com
Objective— Peroxisome proliferator-activated receptor 
(PPAR) ligands reduce lesion formation in animal models of atherosclerosis by mechanisms that have not been defined completely. We hypothesized that PPAR ligands stimulate endothelial-derived nitric oxide release (·NO) to protect the vascular wall.
Methods and Results— The PPAR ligands, 15-deoxy-
12,14-prostaglandin J2 (15d-PGJ2) or ciglitazone, stimulated a PPAR response element-luciferase reporter construct in transfected porcine pulmonary artery endothelial cells (PAECs), demonstrating that PPAR was transcriptionally functional. Treatment with 15d-PGJ2 or ciglitazone significantly increased release of ·NO from PAECs or human aortic endothelial cells and augmented calcium ionophore–induced ·NO release from human umbilical vein endothelial cells measured by chemiluminescence analysis of culture media. Increases in ·NO release caused by treatment with 15d-PGJ2 occurred at 24 hours, but not after 1 to 16 hours, and were abrogated by treatment with the transcriptional inhibitor 
-amanitin. Overexpression of PPAR or treatment with 9-cis retinoic acid also enhanced PAEC ·NO release. Neither 15d-PGJ2 nor ciglitazone altered eNOS mRNA, whereas 15d-PGJ2, but not ciglitazone, decreased eNOS protein.
Conclusions— Taken together, these findings demonstrate that PPAR ligands stimulate ·NO release from endothelial cells derived from multiple vascular sites, through a transcriptional mechanism unrelated to eNOS expression.
Key Words: peroxisome proliferator-activated receptor • endothelium • nitric oxide • nitric oxide synthase • thiazolidinedione
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