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Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Roser, Susanne Roman, Jesse Hart, Craig M. |
| Copyright Year | 2003 |
| Abstract | 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. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/23/1/52.full.pdf?download=true |
| PubMed reference number | 12524224v1 |
| Volume Number | 23 |
| Issue Number | 1 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 15-deoxyprostaglandin J2 9-deoxy-delta-9-prostaglandin D2 Alpha-Amanitin Amanitins Animal Model Atherosclerosis Chemiluminescence Culture Media Endothelial Cells Endothelium Ionophores Ligands Luciferases NOS3 gene Nitric Oxide PPARGC1A wt Allele Pulmonary artery structure Recombinant Interferon-gamma Response Elements Transcription, Genetic Tretinoin Umbilical vein Umbilicus (Anatomy) alitretinoin ciglitazone |
| Content Type | Text |
| Resource Type | Article |
