Inhibition of CINC-1 decreases right ventricular damage caused by experimental pulmonary embolism in rats

John Zagorski, Michael A. Gellar, Maria Obraztsova, Jeffrey Kline, John A. Watts

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7820-7826
Number of pages7
JournalJournal of Immunology
Volume179
Issue number11
StatePublished - Dec 1 2007
Externally publishedYes

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Pulmonary Embolism
Neutrophils
Inflammation
Right Ventricular Dysfunction
CXC Chemokines
Troponin I
Chemotactic Factors
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Peroxidase
Anti-Inflammatory Agents
Cardiovascular Diseases
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Zagorski, J., Gellar, M. A., Obraztsova, M., Kline, J., & Watts, J. A. (2007). Inhibition of CINC-1 decreases right ventricular damage caused by experimental pulmonary embolism in rats. Journal of Immunology, 179(11), 7820-7826.

Inhibition of CINC-1 decreases right ventricular damage caused by experimental pulmonary embolism in rats. / Zagorski, John; Gellar, Michael A.; Obraztsova, Maria; Kline, Jeffrey; Watts, John A.

In: Journal of Immunology, Vol. 179, No. 11, 01.12.2007, p. 7820-7826.

Research output: Contribution to journalArticle

Zagorski, J, Gellar, MA, Obraztsova, M, Kline, J & Watts, JA 2007, 'Inhibition of CINC-1 decreases right ventricular damage caused by experimental pulmonary embolism in rats', Journal of Immunology, vol. 179, no. 11, pp. 7820-7826.
Zagorski, John ; Gellar, Michael A. ; Obraztsova, Maria ; Kline, Jeffrey ; Watts, John A. / Inhibition of CINC-1 decreases right ventricular damage caused by experimental pulmonary embolism in rats. In: Journal of Immunology. 2007 ; Vol. 179, No. 11. pp. 7820-7826.
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