Effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice

doi:10.12047/j.cjap.5579.2018.047

Abstract

Abstract: Objective: To explore the therapeutic effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice.Methods: C57BL/6 mice were randomly divided into sham-operated group, model group and anti-CCL21 monoclonal antibody intervention group, and further randomly divided into 1 d, 3 d,7 d and 21 d subgroups. A mouse model of acute myocardial infarction (AMI) was generated by left anterior descending coronary artery ligation in C57BL/6 mice. Mice in model group were intravenously given isotype-IgG 1.0 mg, mice in anti-CCL21 monoclonal antibody intervention group were intravenously given goat anti-mouse CCL21 monoclonal antibody 1.0 mg at 5 minute and on the 3rd day post-coronary artery ligation. After surgery, C-C motif chemokine receptor 7 (CCR7) expression in myocardium was detected on the 1st, 3rd, 7th day, and the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in myocardium were detected on the 7th day 8 mice per group using Western blot. Serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group were measured on the 1st, 3rd, 7th day post-surgery using ELISA, 8 mice per group. Transthoracic echocardiography was underwent in mice on the 7th and 21th day after surgery using an echocardiography system to evaluate left ventricular function.Results: Compared with sham-operated group, serum levels of CCL21, TNF-α, IL-6, and myocardiac expression of CCR7、MMP-2、MMP-9 in model group were significantly increased (P<0.05). Compared with model group, serum levels of TNF-α and IL-6 and myocardiac expression level of MMP-9 were significantly decreased in anti-CCL21 monoclonal antibody intervention group(P<0.05).Conclusion: Our study indicates that treating with anti-CCL21 monoclonal antibody is involved in preventing cardiac remodeling and protecting left ventricular function post AMI via inhibiting inflammatory response and MMP-9 expression level.

Key words: myocardial infarction, inflammatory response, MMP-9, cardiac remodeling, CCL21, mice

JIANG Yi, YAN Yan-li, BAI Jian-wen. Effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice[J]. CJAP, 2018, 34(3): 197-200.

References

[1] Ueland T, Gullestad L, Nymo SH, et al. Inflammatory cytokines as biomarkers in heart failure[J]. Clin chim acta, 2015, 443:71-77.
[2] Damas JK, Smith C, Oie E, et al. Enhanced expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental atherosclerosis:possible pathogenic role in plaque destabilization[J]. Arterioscler Thromb Vasc Biol, 2007, 27(3):614-620.
[3] Halade GV, Jin YF, Lindsey ML. Matrix metalloproteinase (MMP)-9:a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation[J]. Pharmacol Ther, 2013, 139(1):32-40.
[4] Lindsey ML, Zamilpa R. Temporal and spatial expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases following myocardial infarction[J]. Cardiovasc Ther, 2012, 30(1):31-41.
[5] Li X, Li F, Chu Y, et al. NOD2 deficiency protects against cardiac remodeling after myocardial infarction in mice[J]. Cell Physiol Biochem, 2013, 32(6):1857-1866.
[6] 李健, 陈天萌, 曹剑, 等. 上调血红素氧合酶1对糖尿病心肌梗死大鼠心功能的远期影响[J]. 中国应用生理学杂志, 2014, 30(5):421-426.
[7] van den Borne SW, Cleutjens JP, Hanemaaijer R, et al:Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction[J]. Cardiovasc Pathol, 2009, 18(1):37-43.
[8] Moshal KS, Rodriguez WE, Sen U, et al:Targeted deletion of MMP-9 attenuates myocardial contractile dysfunction in heart failure[J]. Physiol Res, 2008, 57(3):379-384.
[9] 苗婕, 孟凡鹏, 毛士云, 等. ZFP580对大鼠心肌缺血/再灌注后心室重塑的影响[J]. 中国应用生理学杂志, 2017, 33(3):262-266.
[10] 卢彦珍, 王佳, 宋娟, 等. 缺血后处理对缺血/再灌注大鼠心肌基质金属蛋白酶-2表达的影响[J]. 中国应用生理学杂志, 2014, 30(1):81-84.

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