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10.1172/jci.insight.91738

http://scihub22266oqcxt.onion/10.1172/jci.insight.91738
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suck abstract from ncbi


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pmid28352663
      JCI+Insight 2017 ; 2 (6 ): e91738
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  • Retinol-binding protein 7 is an endothelium-specific PPAR? cofactor mediating an antioxidant response through adiponectin #MMPMID28352663
  • Hu C ; Keen HL ; Lu KT ; Liu X ; Wu J ; Davis DR ; Ibeawuchi SC ; Vogel S ; Quelle FW ; Sigmund CD
  • JCI Insight 2017[Mar]; 2 (6 ): e91738 PMID28352663 show ga
  • 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.
  • |Adiponectin/genetics/*metabolism [MESH]
  • |Animals [MESH]
  • |Antioxidants/*metabolism [MESH]
  • |Diet, High-Fat [MESH]
  • |Endothelium, Vascular/*metabolism/physiopathology [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Mice, Knockout [MESH]
  • |Oxidative Stress [MESH]
  • |PPAR gamma/genetics/*metabolism [MESH]
  • |RNA, Messenger/genetics [MESH]


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