Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells.
| Autor: | Calnek DS; Department of Medicine, Veterans Affairs and Emory University, Medical Centers, Decatur, Ga 30033, USA. dcalnek@hotmail.com, Mazzella L, Roser S, Roman J, Hart CM |
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| Jazyk: | angličtina |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2003 Jan 01; Vol. 23 (1), pp. 52-7. |
| DOI: | 10.1161/01.atv.0000044461.01844.c9 |
| Abstrakt: | Objective: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reduce lesion formation in animal models of atherosclerosis by mechanisms that have not been defined completely. We hypothesized that PPARgamma ligands stimulate endothelial-derived nitric oxide release (*NO) to protect the vascular wall. Methods and Results: The PPARgamma ligands, 15-deoxy-Delta(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 PPARgamma 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 alpha-amanitin. Overexpression of PPARgamma 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 PPARgamma ligands stimulate *NO release from endothelial cells derived from multiple vascular sites, through a transcriptional mechanism unrelated to eNOS expression. |
| Databáze: | MEDLINE |
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