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


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 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.
['Hein|Travis W|TW|', 'Qamirani|Erion|E|', 'Ren|Yi|Y|', 'Xu|Xin|X|', 'Thengchaisri|Naris|N|', 'Kuo|Lih|L|']
D000818:Animals D001160:Arterioles D002097:C-Reactive Protein D002351:Carrageenan D002460:Cell Line D003331:Coronary Vessels D004730:Endothelium, Vascular D011464:Epoprostenol D006801:Humans D066298:In Vitro Techniques D009569:Nitric Oxide D017395:Plasminogen Activator Inhibitor 1 D017452:Receptors, IgG D051127:Scavenger Receptors, Class E D013481:Superoxides D013552:Swine D014664:Vasodilation
vasodilation oxidative stress nitric oxide