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Native C-reactive protein induces endothelial dysfunction in ApoE-/- mice: implications for iNOS and reactive oxygen species.

Abstract：

OBJECTIVE:In addition to being a risk marker for cardiovascular disease, recent data suggests that C-reactive protein (CRP) induces endothelial dysfunction and promotes oxidative stress. We evaluated the effects of two conformers of CRP (pentameric, or native [nCRP], versus monomeric, or modified [mCRP]) on vessel function and production of reactive oxygen species (ROS) in an in-vivo model of atherosclerosis. METHODS AND RESULTS:Female ApoE(-/-) mice, fed a "western-type" diet, were treated with either human nCRP or mCRP (2.5mg/kg s.c., weekly) or saline for 8 weeks. Endothelium-dependent and endothelium-independent vascular functions were assessed in isolated aortic rings under isometric conditions. Production of ROS in aortic rings was measured by electron spin resonance (ESR). Endothelium-dependent relaxation was impaired in nCRP-treated but not in mCRP-treated ApoE(-/-) mice. This impairment was reversed by preincubation with an inhibitor of inducible nitric oxide synthase (iNOS). Endothelium-independent relaxation, and iNOS and endothelial NOS (eNOS) protein expressions were similar among all groups. ESR experiments revealed lesser amounts of superoxide in the nCRP group as compared to the saline group, which is consistent with an increased transformation of NO to peroxynitrite. CONCLUSIONS:nCRP can facilitate cardiovascular disease through impairment of endothelium-dependent vasoreactivity, in a manner that involves increased iNOS activity and a potential for increased peroxynitrite formation.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Schwedler SB,Kuhlencordt PJ,Ponnuswamy PP,Hatiboglu G,Quaschning T,Widder J,Wanner C,Potempa LA,Galle J

doi

10.1016/j.atherosclerosis.2007.06.013

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

e76-84

issue

2

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(07)00386-3

journal_volume

195

pub_type

杂志文章

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