Retinol-binding protein 7 is an endothelium-specific PPAR? cofactor mediating an antioxidant response through adiponectin.

ABSTRACT: Impaired PPAR? activity in endothelial cells causes oxidative stress and endothelial dysfunction which causes a predisposition to hypertension, but the identity of key PPAR? target genes that protect the endothelium remain unclear. Retinol-binding protein 7 (RBP7) is a PPAR? 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 PPAR? 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 PPAR? in the endothelium through adiponectin, and RBP7 is an endothelium-specific PPAR? target and regulator of PPAR? activity.

SUBMITTER: Hu C 

PROVIDER: S-EPMC5358481 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature