Selective activation of lectin-like oxidized low-density lipoprotein receptor-1 mediates C-reactive protein-evoked endothelial vasodilator dysfunction in coronary arterioles. Academic Article uri icon


  • RATIONALE: Studies in cultured endothelium implicate that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or Fc 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. METHODS AND 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 g/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 -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.

published proceedings

  • Circ Res

author list (cited authors)

  • Hein, T. W., Qamirani, E., Ren, Y. i., Xu, X., Thengchaisri, N., & Kuo, L.

citation count

  • 26

complete list of authors

  • Hein, Travis W||Qamirani, Erion||Ren, Yi||Xu, Xin||Thengchaisri, Naris||Kuo, Lih

publication date

  • January 2014