Maekawa Yuichiro, Anzai Toshihisa, Yoshikawa Tsutomu, Sugano Yasuo, Mahara Keitaro, Kohno Takashi, Takahashi Toshiyuki, Ogawa Satoshi
Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
J Am Coll Cardiol. 2004 Oct 6;44(7):1510-20. doi: 10.1016/j.jacc.2004.05.083.
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.
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.
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 microg/kg/day for 7 consecutive days) (MI/Ro) or saline (MI/C).
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)-beta1 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.
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.
我们试图确定粒细胞巨噬细胞集落刺激因子（GM-CSF）诱导对心肌梗死后（MI）重塑的影响，特别是与炎症反应和心肌纤维化的关系。
粒细胞巨噬细胞集落刺激因子通过促进单核细胞生成以及单核细胞和巨噬细胞浸润到受损组织中来改变伤口愈合；然而，GM-CSF诱导对梗死愈合过程和心肌纤维化的影响尚不清楚。
通过结扎左冠状动脉在Wistar大鼠中建立MI模型。将MI动物随机分为接受GM-CSF诱导剂（罗莫肽200μg/kg/天，连续7天）（MI/Ro）或生理盐水（MI/C）。
第14天的超声心动图和血流动力学研究显示，与MI/C相比，MI/Ro的左心室（LV）舒张末期内径增加、缩短分数降低、LV舒张末期压力升高以及LV等容压力最大上升速率降低。免疫印迹显示，与MI/C相比，MI后第3天梗死部位转化生长因子（TGF）-β1的表达在MI/Ro中降低。在梗死部位，与MI/C相比，MI/Ro中第3天TGF-β1、I型和III型胶原信使核糖核酸（mRNA）表达以及第7天的胶原含量降低，伴有明显的梗死扩展。在MI/Ro中，第7天梗死部位的单核细胞趋化蛋白-1 mRNA水平和单核细胞衍生巨噬细胞（ED-1阳性）的浸润程度高于MI/C。
罗莫肽诱导的GM-CSF在MI早期促进梗死区域单核细胞募集和不适当的胶原合成，从而促进梗死扩展。
