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Atherosclerosis. 2009 Sep;206(1):61-8. doi: 10.1016/j.atherosclerosis.2009.02.002. Epub 2009 Feb 12.

Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo.

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1
Department of Surgery, Scott & White Memorial Hospital, College of Medicine, Texas A&M Health Science Center, Temple, TX, USA.

Abstract

BACKGROUND AND OBJECTIVE:

Elevated C-reactive protein (CRP) levels are associated with increased cardiovascular events and endothelial dysfunction. We have previously shown that CRP decreases endothelial nitric oxide synthase (eNOS) activity in endothelial cells and inhibits endothelium-dependent nitric oxide (NO)-mediated vasodilation in vitro. Herein, we examined the effect of in vivo administration of CRP on endothelial function and underlying mechanisms in a valid animal model.

METHODS:

Sprague-Dawley rats were injected intraperitoneally daily for 3 days with human CRP or human serum albumin (HuSA) at 20 mg/kg body weight. On day 4, mesenteric arterioles were isolated and pressurized for vasomotor study and aortic tissue was subjected to biochemical and molecular analysis.

RESULTS:

Dilation of mesenteric arterioles to acetylcholine but not to sodium nitroprusside was significantly reduced following CRP treatment. The eNOS activity, eNOS dimer/monomer ratio, tetrahydrobiopterin levels, and protein expression of GTPCH1 were significantly lower in aortic tissue homogenates from CRP-treated than HuSA-treated rats. CRP treatment also resulted in increased dihydroethidium staining for superoxide in aortic endothelium and membrane translocation of p47phox, a regulatory subunit of NADPH oxidase.

CONCLUSION:

Our data provide novel evidence for the detrimental action of CRP in vivo by impairing eNOS-dependent vasodilation and uncoupling of eNOS.

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