Abstract
Abstract 21: Retinol-binding Protein 7 (RBP7), a Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Target Gene, is a Novel Regulator of Endothelial Function
Hypertension (Dallas, Tex. 1979), Vol.62(suppl_1), p.A21
09/2013
DOI: 10.1161/hyp.62.suppl_1.A21
Abstract
PPARG, a ligand-activated transcription factor, in the endothelium regulates vascular function and blood pressure, through mechanisms that remain poorly defined. Endothelial-specific expression of dominant negative (DN) PPARG (E-V290M) caused endothelial dysfunction when combined with a high fat diet (HFD). RBP7 is an intracellular retinoid binding protein belonging to the family of fatty acid-binding proteins and a PPARG target gene. RBP7 expression in aorta is induced by rosiglitazone and repressed by DN PPARG, and its level of expression is highly correlated with PPARG in other tissues. RBP7 is also expressed in endothelium. We hypothesize that RBP7 may mediate some vascular protective effects of PPARG during HFD. We examined vascular responses in basilar artery (BA, pressurized myograph) and carotid artery (CA, wire myograph) of RBP7-deficient (KO), heterozygous (HZ), and wild type (WT) mice fed normal chow diet (ND) or HFD for 8 or 20 wks. Weight gain was similar in all three HFD-fed groups and was higher than ND-fed mice. There was no difference in the endothelium-dependent, acetylcholine (ACh)-induced relaxation in either BA or CA of any group under ND. Following 8 wks HFD, BA from KO mice exhibited impaired relaxation to ACh compared to control mice (at 100μM: 33±7% KO vs 73±7% HZ vs 83±10% WT, p<0.05). A normal response was observed to the nitric oxide donor, nitroprusside (SNP). An impaired ACh-, but not SNP- or papaverine-induced relaxation was observed in CA of KO mice after 20 wks of HFD (ACh 30μM: 49±6% KO vs 61±3% HZ vs 70±4% WT, p<0.05). No differences were found in phenylephrine- and endothelin-1-induced contractions in CA in any group. Pre-incubation of BA for 30 minutes with the superoxide scavengers tempol (1mM) or PEG-superoxide dismutase (PEG-SOD, 100 U/ml) completely restored ACh-induced relaxation to normal (ACh at 100μM: 79±7% Tempol-KO; 75±12% PEG-SOD-KO; 81±11% WT). This phenotype was very similar to that observed in HFD fed E-V290M mice. We conclude that loss of RBP7 causes endothelial dysfunction in response to a HFD through a mechanism involving oxidative stress. These findings provide the first evidence that RBP7 plays a protective role in the endothelium, which might be related to the endothelial protective effects of PPARG.
Details
- Title: Subtitle
- Abstract 21: Retinol-binding Protein 7 (RBP7), a Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Target Gene, is a Novel Regulator of Endothelial Function
- Creators
- Chunyan Hu - University of IowaKo-Ting Lu - University of IowaMary L Modrick - University of IowaSilke Vogel - Duke NUS Graduate Medical SchoolFrank M Faraci - University of IowaCurt D Sigmund - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.62(suppl_1), p.A21
- DOI
- 10.1161/hyp.62.suppl_1.A21
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2013
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984304751302771
Metrics
3 Record Views