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The Journal of Immunology, 2007, 179: 7820-7826.
Copyright © 2007 by The American Association of Immunologists, Inc.

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Inhibition of CINC-1 Decreases Right Ventricular Damage Caused by Experimental Pulmonary Embolism in Rats1

John Zagorski, Michael A. Gellar, Maria Obraztsova, Jeffrey A. Kline and John A. Watts2

Department of Emergency Medicine, James G. Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203

Right ventricular (RV) dysfunction is a strong risk factor for poor clinical outcome following pulmonary embolism (PE), the third most prevalent cardiovascular disease. Previous studies in our laboratory demonstrated that RV failure during PE is mediated, in part, by neutrophil-dependant cardiac inflammation. In this study we use DNA microarray analysis of gene expression to demonstrate that PE results in increased expression of the CXC chemokines CINC-1 and CINC-2 between 6 and 18 h after the start of PE in a rat model of PE. Neutrophils accumulate in RV tissue by 18 h, and this inflammation is associated with decreased right heart function. Treatment of rats with Abs to CINC-1 significantly suppressed neutrophil accumulation in RVs during PE (52% reduction in tissue myeloperoxidase) and ameliorated RV failure. In addition, plasma concentration of cardiac troponin I, an established diagnostic marker for cardiac damage, was reduced by 90%. These results suggest that selective anti-inflammatory therapies targeted at neutrophil chemoattractants will reduce cardiac inflammation and reduce RV damage in the setting of PE.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported in part by a generous grant from the Carolinas Medical Center Education and Grants Committee (to J.Z.).

2 Address correspondence and reprint requests to Dr. John A. Watts, Department of Emergency Medicine, Carolinas Medical Center, Cannon Research Center, Room 302, 1542 Garden Terrace, Charlotte, NC 28203. E-mail address: jwatts{at}carolinas.org

3 Abbreviations used in this paper: PE, pulmonary embolism; BCA, bicinchoninic acid; CINC, cytokine-induced neutrophil chemoattractant; LV, left ventricular; MMP, matrix metalloproteinase; MPO, myeloperoxidase; RV, right ventricular.




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J. Zagorski, N. Sanapareddy, M. A. Gellar, J. A. Kline, and J. A. Watts
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats
Physiol Genomics, June 10, 2008; 34(1): 101 - 111.
[Abstract] [Full Text] [PDF]




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