Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-ReperfusionHartman, M. H. T., Vreeswijk-Baudoin, I., Groot, H. E., van de Kolk, K. W. A., de Boer, R. A., Leach, I. M., Vliegenthart, R., Sillje, H. H. W. & van der Harst, P., 9-Dec-2016, In : PLoS ONE. 11, 12, 11 p., e0167195.
Research output: Contribution to journal › Article › Academic › peer-review
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).
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.
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.
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.
|Number of pages||11|
|Publication status||Published - 9-Dec-2016|
- RHEUMATOID-ARTHRITIS, IL-6 RECEPTOR, ANTIBODY, DISEASE, HEART, MICE, MECHANISMS, INFARCTION, CARDIOMYOCYTES, TOCILIZUMAB
Hartman, H. (Creator), Baudoin, I. (Creator), Groot, H. (Creator), de Kolk, K. W. V. (Creator), Boer, de, R. (Creator), Mateo Leach, I. (Creator), Vliegenthart, R. (Creator), Sillje, H. (Creator), Harst, van der, P. (Creator), University of Groningen, 18-Nov-2016