advertisement
Abstract #20995 Published in IGR 10-2
C-Reactive protein inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production
Nagaoka T; Kuo L; Ren Y; Yoshida A; Hein TWInvestigative Ophthalmology and Visual Science 2008; 49: 2053-2060
PURPOSE: Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, clinical studies have implicated that elevated CRP is an independent risk factor for diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP on ocular microvascular reactivity remains unknown. The authors examined whether CRP can affect endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the CRP-mediated effect. METHODS: Porcine retinal arterioles (internal diameter, 71 ± 2 μm) were isolated and pressurized without flow for in vitro study. Diameter changes were recorded using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production. RESULTS: Intraluminal treatment with a clinically relevant concentration of CRP (7 mug/mL, 60 minutes) significantly attenuated arteriolar dilation to endothelium-dependent NO-mediated agonists bradykinin and A23187 but not to endothelium-independent NO donor sodium nitroprusside. In the presence of superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, simvastatin, or Rho-kinase inhibitor Y-27632, the detrimental effect of CRP on bradykinin-induced dilation was prevented. DHE staining showed that CRP produced TEMPOL-sensitive superoxide production in the arteriolar endothelium. CONCLUSIONS: CRP inhibits endothelium-dependent NO-mediated dilation in retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase and RhoA/Rho-kinase activation. By impairing endothelium-dependent NO-mediated vasoreactivity, CRP can potentially facilitate the development of retinal vascular diseases. In addition, statins are beneficial by preserving endothelial function, possibly through inactivation of the RhoA/Rho-kinase pathway.
Classification:
6.11 Bloodflow measurements (Part of: 6 Clinical examination methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)