Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin
| Autor: | Deborah R. Davis, Curt D. Sigmund, Jing Wu, Chunyan Hu, Xuebo Liu, Henry L. Keen, Stella-Rita C Ibeawuchi, Ko-Ting Lu, Silke Vogel, Frederick W. Quelle |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endothelium 030204 cardiovascular system & hematology Diet High-Fat medicine.disease_cause Antioxidants Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Glucose homeostasis RNA Messenger Endothelial dysfunction Mice Knockout Adiponectin Chemistry Retinol-Binding Proteins Cellular General Medicine medicine.disease Angiotensin II Mice Inbred C57BL PPAR gamma Oxidative Stress Retinol binding protein 030104 developmental biology Endocrinology medicine.anatomical_structure Biochemistry Endothelium Vascular Rosiglitazone Oxidative stress Research Article medicine.drug |
| Zdroj: | JCI Insight. 2 |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|