title: Selective activation of lectin-like oxidized low-density lipoprotein receptor-1 mediates C-reactive protein-evoked endothelial vasodilator dysfunction in coronary arterioles.
abstract: BACKGROUND
  Studies in cultured endothelium implicate that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or Fcγ receptor II (CD32) contributes to the proatherogenic effects of C-reactive protein (CRP). However, the identity of the receptors linking to deleterious actions of CRP in vasomotor regulation remains unknown.
  
  
  OBJECTIVE
  We tested the hypothesis that LOX-1 contributes to adverse effects of CRP on endothelium-dependent vasomotor function in resistance arterioles.
  
  
  RESULTS
  Porcine coronary arterioles were isolated for vasoreactivity study, dihydroethidium fluorescence staining of superoxide, immunohistochemical localization of receptors, immunoprecipitation of receptor/CRP interaction, and protein blot. Intraluminal treatment of pressurized arterioles with a pathophysiological level of CRP (7 µg/mL; 60 minutes) attenuated endothelium-dependent nitric oxide-mediated and prostacyclin-mediated dilations to serotonin and arachidonic acid, respectively. LOX-1 and CD32 were detected in the endothelium of arterioles. Blockade of LOX-1 with either pharmacological antagonist κ-carrageenan or anti-LOX-1 antibody prevented the detrimental effect of CRP on vasodilator function, whereas anti-CD32 antibody treatment was ineffective. Denudation of endothelium and blockade of LOX-1 but not CD32 prevented CRP-induced elevation of superoxide in the vessel wall. CRP was coimmunoprecipitated with LOX-1 and CD32 from CRP-treated arterioles. Similarly, LOX-1 and CD32 blockade prevented CRP-induced arteriolar expression of plasminogen activator inhibitor-1, a thrombogenic protein.
  
  
  CONCLUSIONS
  CRP elicits endothelium-dependent oxidative stress and compromises nitric oxide-mediated and prostacyclin-mediated vasomotor function via LOX-1 activation. In contrast, both LOX-1 and CD32 mediate plasminogen activator inhibitor-1 upregulation in arterioles by CRP. Thus, activation of LOX-1 and CD32 may contribute to vasomotor dysfunction and proatherogenic actions of CRP, respectively.
authors.affiliation: From the Departments of Surgery (T.W.H., Y.R., L.K.) and Medical Physiology (E.Q., X.X., N.T., L.K.), College of Medicine, Texas A&M Health Science Center, Scott & White Healthcare, Temple; and Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand (N.T.).
authors.forename: Travis W
authors.initials: TW
authors.lastname: Hein
authors.forename: Erion
authors.initials: E
authors.lastname: Qamirani
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Naris
authors.initials: N
authors.lastname: Thengchaisri
authors.forename: Lih
authors.initials: L
authors.lastname: Kuo
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology; D002097:C-Reactive Protein / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014664:Vasodilation
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D017452:Receptors, IgG; D051127:Scavenger Receptors, Class E; D013481:Superoxides; D009569:Nitric Oxide; D002351:Carrageenan; D002097:C-Reactive Protein; D011464:Epoprostenol
keywords: nitric oxide; oxidative stress; vasodilation