Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction
Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction
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DOI：
10.1016/j.jacc.2004.05.083
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发表时间：
2004-10-06
影响因子：
24
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Maekawa, Y;Anzai, T;Ogawa, S
我们试图确定粒细胞-巨噬细胞集落刺激因子（GM-CSF）诱导对心肌梗死（MI）后重塑的影响，特别是与炎症反应和心肌纤维化的关系。方法结扎Wistar大鼠左冠状动脉建立心肌梗死模型，用放射免疫法测定心肌纤维化程度。MI动物随机接受GM-CSF诱导剂（romurtide 200 μ g/kg/day，连续7天）（MI/Ro）或生理盐水（MI/C）。结果第14天超声心动图和血流动力学研究显示，与MI/C相比，MI/Ro组左心室舒张末期内径增加，缩短分数降低，左心室舒张末期压升高，左心室等容压最大发展速率降低。免疫印迹显示，与MI/C相比，MI/Ro中MI后第3天梗死部位转化生长因子（TGF）-β 1的表达减少。在梗死部位，与MI/C相比，MI/Ro组第3天TGF-β 1、I型和III型胶原信使核糖核酸（mRNA）表达以及第7天胶原含量均降低，这与明显的梗死扩展相关。在MI/Ro中，单核细胞趋化蛋白-1 mRNA水平和单核细胞衍生的巨噬细胞（艾德-1-阳性）的浸润程度在第7天的梗死部位比MI/C中的那些更大。结论：GM-CSF诱导促进梗死扩大与促进单核细胞募集和不适当的胶原蛋白合成在MI的早期阶段的梗死区域。（美国科尔心脏病学杂志2004;44：1510-20）（C）美国心脏病学会基金会2004年。
OBJECTIVES We sought to determine the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) induction on post-myocardial infarction (MI) remodeling, especially in relation to the inflammatory response and myocardial fibrosis.BACKGROUND Granulocyte-macrophage colony-stimulating factor modifies wound healing by promoting monocytopoiesis and infiltration of monocytes and macrophages into injured tissue; however, the effect of GM-CSF induction on the infarct healing process and myocardial fibrosis is unclear.METHODS A model of MI was produced in Wistar rats by ligation of the left coronary artery. The MI animals were randomized to receive GM-CSF inducer (romurtide 200 mug/kg/day for 7 consecutive days) (MI/Ro) or saline (MI/C).RESULTS Echocardiographic and hemodynamic studies on day 14 revealed increased left ventricular (LV) end-diastolic dimension, decreased fractional shortening, elevated LV end-diastolic pressure, and decreased LV maximum rate of isovolumic pressure development in MI/Ro compared with MI/C. Immunoblotting showed that expression of transforming growth factor (TGF)-betal in the infarcted site on day 3 after MI was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-beta1, collagen type I and type III messenger ribonucleic acid (mRNA) expression on day 3, and collagen content on day 7 were reduced in MI/Ro compared with MI/C, in association with marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level and the degree of infiltration of monocyte-derived macrophages (ED-1-positive) were greater in the infarcted site on day 7 than those in MI/C.CONCLUSIONS The GM-CSF induction by romurtide facilitated infarct expansion in association with the promotion of monocyte recruitment and inappropriate collagen synthesis in the infarcted region during the early phase of MI. (J Am Coll Cardiol 2004;44:1510-20) (C) 2004 by the American College of Cardiology Foundation.