[HTML][HTML] Inhibition of interleukin-6 receptor in a murine model of myocardial ischemia-reperfusion
MHT Hartman, I Vreeswijk-Baudoin, HE Groot… - PloS one, 2016 - journals.plos.org
MHT Hartman, I Vreeswijk-Baudoin, HE Groot, KWA van de Kolk, RA de Boer, I Mateo Leach…
PloS one, 2016•journals.plos.orgBackground 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 0.5 mg/mouse …
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 0.5 mg/mouse …
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.
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