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, van der Harst Pim
University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, the Central Animal Facility, Groningen, the Netherlands.
PLoS One. 2016 Dec 9;11(12):e0167195. doi: 10.1371/journal.pone.0167195. eCollection 2016.
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.
白细胞介素-6（IL-6）水平在心肌梗死中上调。近期数据表明白细胞介素-6受体（IL-6R）在冠心病中起因果作用。我们评估了在缺血再灌注（I/R）小鼠模型中，单克隆抗体（MR16-1）阻断IL-6R是否能防止心脏发生不良左心室重构。
C57/BL6小鼠接受I/R损伤（左冠状动脉结扎45分钟）或假手术，然后在再灌注前5分钟接受MR16-1（2mg/小鼠），并在四周内每周接受0.5mg/小鼠，或接受对照IgG治疗。四周后进行心脏磁共振成像（CMR）和血流动力学测量以确定心脏功能。
I/R导致左心室扩张和左心室射血分数（LVEF）降低。然而，与IgG组相比，MR16-1治疗组的LVEF显著更低（分别为28±4%对35±6%，p = 0.02；假手术组分别为45±6%对43±4%，p =无显著性差异）。MR16-1组和IgG组之间的心脏舒张功能（通过dP/dT评估）无显著差异。此外，各组之间在组织学心肌纤维化、梗死面积和心肌细胞肥大方面未观察到差异。
在I/R损伤后直接开始用单克隆MR16-1抗体阻断IL-6R受体四周，并不能防止小鼠心脏重构过程，反而与不良心脏重构过程的恶化相关。
