Journal article
Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin
JCI insight, Vol.2(6), pp.e91738-e91738
03/23/2017
DOI: 10.1172/jci.insight.91738
PMCID: PMC5358481
PMID: 28352663
Abstract
Impaired PPARγ activity in endothelial cells causes oxidative stress and endothelial dysfunction which causes a predisposition to hypertension, but the identity of key PPARγ target genes that protect the endothelium remain unclear. Retinol-binding protein 7 (RBP7) is a PPARγ target gene that is essentially endothelium specific. Whereas RBP7-deficient mice exhibit normal endothelial function at baseline, they exhibit severe endothelial dysfunction in response to cardiovascular stressors, including high-fat diet and subpressor angiotensin II. Endothelial dysfunction was not due to differences in weight gain, impaired glucose homeostasis, or hepatosteatosis, but occurred through an oxidative stress–dependent mechanism which can be rescued by scavengers of superoxide. RNA sequencing revealed that RBP7 was required to mediate induction of a subset of PPARγ target genes by rosiglitazone in the endothelium including adiponectin. Adiponectin was selectively induced in the endothelium of control mice by high-fat diet and rosiglitazone, whereas RBP7 deficiency abolished this induction. Adiponectin inhibition caused endothelial dysfunction in control vessels, whereas adiponectin treatment of RBP7-deficient vessels improved endothelium-dependent relaxation and reduced oxidative stress. We conclude that RBP7 is required to mediate the protective effects of PPARγ in the endothelium through adiponectin, and RBP7 is an endothelium-specific PPARγ target and regulator of PPARγ activity.
Details
- Title: Subtitle
- Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin
- Creators
- Chunyan Hu - Department of PharmacologyHenry L Keen - Department of PharmacologyKo-Ting Lu - Department of PharmacologyXuebo Liu - Department of PharmacologyJing Wu - Department of PharmacologyDeborah R Davis - Department of PharmacologyStella-Rita C Ibeawuchi - Department of PharmacologySilke Vogel - Duke-NUS Medical School, Singapore, SingaporeFrederick W Quelle - Department of PharmacologyCurt D Sigmund - Department of Pharmacology
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.2(6), pp.e91738-e91738
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/jci.insight.91738
- PMID
- 28352663
- PMCID
- PMC5358481
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Language
- English
- Date published
- 03/23/2017
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Neuroscience and Pharmacology; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9984040276902771
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