Published online before print August 19, 2004, doi: 10.1161/01.ATV.0000142807.92781.d9
© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
C-Reactive Protein-Induced In Vitro Vasorelaxation Is an Artefact Caused by the Presence of Sodium Azide in Commercial Preparations
From the Department of Pharmacology, Therapeutics, and Toxicology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, United Kingdom.
Correspondence to Dr Carmen W. van den Berg, Department of Pharmacology, Therapeutics, and Toxicology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom. E-mail vandenbergcw{at}cardiff.ac.uk
Objective— Although C-reactive protein (CRP) is increasingly recognized as an independent risk factor for acute myocardial events, recent evidence suggests that it can directly induce vasorelaxation. This study aimed to investigate the mechanism of this CRP-induced response.
Methods and Results— Isometric tension recordings were used to measure endothelium-dependent and endothelium-independent vascular smooth muscle relaxation in isolated rabbit aortic rings. CRP generated in-house by genetic engineering and expressed in Chinese hamster ovary cells, CRP purified from ascites, and CRP obtained from commercial sources were assessed for vasorelaxing properties. Only the commercial CRP preparation induced vasorelaxation; more than half maximal relaxation was observed at 0.025 µg/mL and maximum relaxation attained at 0.25 µg/mL. Commercial CRP contains high levels of sodium azide, a well-known vasorelaxant. Removal of this agent by dialysis abolished the vasodilatory effect of commercial CRP. Sodium azide alone at concentrations equivalent to that present in the commercial CRP produced a near-identical relaxation pattern to the undialyzed commercial product.
Conclusions— CRP has no vasorelaxant properties per se, and the reported vasorelaxant ability of CRP is an artifact caused by sodium azide present in commercial preparations of this agent.
We constructed a congenic mouse strain in which chromosome 15 interval from MRL/MpJ is placed on the genetic background of BALB/c. Analysis of the congenic strain showed that the underlying gene, termed Hyplip2, increases plasma cholesterol and triglyceride levels, accompanied by a dramatic 
30-fold increase in atherosclerotic lesions.
Key Words: C-reactive protein • sodium azide • vasorelaxation
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