Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion

Minke H. T. Hartman, Inge Vreeswijk-Baudoin, Hilde E. Groot, Kees W. A. van de Kolk, Rudolf A. de Boer, Irene Mateo Leach*, Rozemarijn Vliegenthart, Herman H. W. Sillje, Pim van der Harst

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

33 Citaten (Scopus)
345 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummere0167195
Aantal pagina's11
TijdschriftPLoS ONE
Volume11
Nummer van het tijdschrift12
DOI's
StatusPublished - 9-dec.-2016

Vingerafdruk

Duik in de onderzoeksthema's van 'Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion'. Samen vormen ze een unieke vingerafdruk.

Citeer dit