Abstract:
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 microm) 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 microg/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.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Nagaoka T,Kuo L,Ren Y,Yoshida A,Hein TWdoi
10.1167/iovs.07-1387subject
Has Abstractpub_date
2008-05-01 00:00:00pages
2053-60issue
5eissn
0146-0404issn
1552-5783pii
49/5/2053journal_volume
49pub_type
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journal_title:Investigative ophthalmology & visual science
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