title: Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice.
abstract: BACKGROUND
  We hypothesized that atherosclerosis inhibits NO-mediated endothelium-dependent dilation of coronary arterioles through interaction of ox-LDL with its receptor, LOX-1, through the production of O2ÿ- in endothelial cells.
  
  
  RESULTS
  We assessed the role of ox-LDL in endothelial dysfunction in a murine model of atherosclerosis (ApoE KO mice). Coronary arterioles from WT control and ApoE KO mice were isolated and pressurized without flow. Although dilation of vessels to endothelium-independent vasodilator SNP was not altered between ApoE KO and WT mice, dilation to the endothelium-dependent agonist, ACh was reduced in ApoE KO versus WT mice. Impaired vasodilation to ACh in ApoE KO mice is partially restored by NAD(P)H oxidase inhibitor, apocynin or DPI. Messenger RNA expression for NAD(P)H oxidases was higher in ApoE KO mice than that in WT and anti-LOX-1 treated ApoE KO mice. Anti-LOX-1, given in vivo, restored NO-mediated coronary arteriolar dilation in ApoE KO mice, but did not affect the endothelium-dependent vasodilation in controls.
  
  
  CONCLUSIONS
  These results suggest that ox-LDL impairs endothelium-dependent NO-mediated dilation of coronary arterioles by activation of a signaling cascade involving LOX-1 and NAD(P)H oxidase expression.
authors.affiliation: Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA.
authors.forename: Xiangbin
authors.initials: X
authors.lastname: Xu
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Potter
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Cao
authors.forename: Cuihua
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency*; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004579:Electron Transport; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000276:immunology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000906:Antibodies; D001057:Apolipoproteins E; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D000109:Acetylcholine