| First Author | Hu C | Year | 2017 |
| Journal | JCI Insight | Volume | 2 |
| Issue | 6 | Pages | e91738 |
| PubMed ID | 28352663 | Mgi Jnum | J:290294 |
| Mgi Id | MGI:6442524 | Doi | 10.1172/jci.insight.91738 |
| Citation | Hu C, et al. (2017) Retinol-binding protein 7 is an endothelium-specific PPARgamma cofactor mediating an antioxidant response through adiponectin. JCI Insight 2(6):e91738 |
| abstractText | Impaired PPARgamma activity in endothelial cells causes oxidative stress and endothelial dysfunction which causes a predisposition to hypertension, but the identity of key PPARgamma target genes that protect the endothelium remain unclear. Retinol-binding protein 7 (RBP7) is a PPARgamma 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 PPARgamma 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 PPARgamma in the endothelium through adiponectin, and RBP7 is an endothelium-specific PPARgamma target and regulator of PPARgamma activity. |
