Interference with PPARγ in endothelium accelerates angiotensin II-induced endothelial dysfunction
| Autor: | Frank M. Faraci, Curt D. Sigmund, Deborah R. Davis, Chunyan Hu, Ko-Ting Lu, Masashi Mukohda |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Physiology Peroxisome proliferator-activated receptor Blood Pressure 030204 cardiovascular system & hematology Ligands Antioxidants Mice 0302 clinical medicine Heart Rate Superoxides Endothelial dysfunction Receptor chemistry.chemical_classification Angiotensin II NF-kappa B Anatomy Catalase Carotid Arteries medicine.anatomical_structure cardiovascular system Peroxisome proliferator-activated receptor gamma medicine.medical_specialty Endothelium Mice Transgenic Biology Diet High-Fat Real-Time Polymerase Chain Reaction 03 medical and health sciences Internal medicine Genetics medicine Animals Superoxide Dismutase NFKB1 medicine.disease Acetylcholine Mice Inbred C57BL PPAR gamma Oxidative Stress Spectrometry Fluorescence 030104 developmental biology Endocrinology chemistry Nuclear receptor Endothelium Vascular Reactive Oxygen Species |
| Zdroj: | Physiological Genomics. 48:124-134 |
| ISSN: | 1531-2267 1094-8341 |
| Popis: | The ligand activated nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) in the endothelium regulates vascular function and blood pressure (BP). We previously reported that transgenic mice (E-V290M) with selectively targeted endothelial-specific expression of dominant negative PPARγ exhibited endothelial dysfunction when treated with a high-fat diet, and exhibited an augmented pressor response to angiotensin II (ANG II). We hypothesize that interference with endothelial PPARγ would exacerbate ANG II-induced endothelial dysfunction. Endothelial function was examined in E-V290M mice infused with a subpressor dose of ANG II (120 ng·kg−1·min−1) or saline for 2 wk. ANG II infusion significantly impaired the responses to the endothelium-dependent agonist acetylcholine both in basilar and carotid arteries from E-V290M but not NT mice. This impairment was not due to increased BP, which was not significantly different in ANG II-infused E-V290M compared with NT mice. Superoxide levels, and expression of the pro-oxidant Nox2 gene was elevated, whereas expression of the anti-oxidant genes Catalase and SOD3 decreased in carotid arteries from ANG II-infused E-V290M mice. Increased p65 and decreased Iκ-Bα suggesting increased NF-κB activity was also observed in aorta from ANG II-infused E-V290M mice. The responses to acetylcholine were significantly improved both in basilar and carotid arteries after treatment with Tempol (1 mmol/l), a scavenger of superoxide. These findings provide evidence that interference with endothelial PPARγ accelerates ANG II-mediated endothelial dysfunction both in cerebral and conduit arteries through an oxidative stress-dependent mechanism, suggesting a role for endothelial PPARγ in protecting against ANG II-induced endothelial dysfunction. |
| Databáze: | OpenAIRE |
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