1. Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion.
- Author
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Hartman, Minke H. T., Vreeswijk-Baudoin, Inge, Groot, Hilde E., van de Kolk, Kees W. A., de Boer, Rudolf A., Mateo Leach, Irene, Vliegenthart, Rozemarijn, Sillje, Herman H. W., and van der Harst, Pim
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INTERLEUKIN-6 receptors , *CORONARY disease , *REPERFUSION , *HYPERTROPHY , *LABORATORY rodents - Abstract
Background: Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the heart from adverse left ventricular remodeling in a mouse model of ischemia-reperfusion (I/R). Methods: CJ57/BL6 mice underwent I/R injury (left coronary artery ligation for 45 minutes) or sham surgery, and thereafter received MR16-1 (2mg/mouse) 5 minutes before reperfusion and 0.5mg/mouse weekly during four weeks, or control IgG treatment. Cardiac Magnetic Resonance Imaging (CMR) and hemodynamic measurements were performed to determine cardiac function after four weeks. Results: I/R caused left ventricular dilatation and a decrease in left ventricular ejection fraction (LVEF). However, LVEF was significantly lower in the MR16-1 treatment group compared to the IgG group (28±4% vs. 35±6%, p = 0.02; sham 45±6% vs. 43±4%, respectively; p = NS). Cardiac relaxation (assessed by dP/dT) was not significantly different between the MR16-1 and IgG groups. Also, no differences were observed in histological myocardial fibrosis, infarct size and myocyte hypertrophy between the groups. Conclusion: Blockade of the IL-6R receptor by the monoclonal MR16-1 antibody for four weeks started directly after I/R injury did not prevent the process of cardiac remodeling in mice, but rather associated with a deterioration in the process of adverse cardiac remodeling. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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