Effects of G-CSF on cardiac remodeling and arterial hyperplasia in rats
Effects of G-CSF on cardiac remodeling and arterial hyperplasia in rats
复制标题
DOI：
10.1016/j.ejphar.2006.08.006
复制
发表时间：
2006-11-07
影响因子：
5
通讯作者：
Saito, Satoshi
中科院分区：
文献类型：
--
作者：
Li, Yuxin;Fukuda, Noboru;Saito, Satoshi
尽管粒细胞集落刺激因子（G-CSF）已被证明可以预防急性心肌梗死后的心脏重塑，但G-CSF治疗急性心肌梗死的机制和安全性仍存在争议。本研究的目的是在大鼠模型中研究 G-CSF 对急性心肌梗塞有益作用的机制，并确定 G-CSF 治疗是否会加剧急性心肌梗塞后受损动脉的血管重塑。 Sprague-Dawley 大鼠接受来自绿色荧光蛋白 (GFP) 转基因大鼠的移植骨髓细胞。结扎左冠状动脉诱发急性心肌梗死。 24小时后，用球囊导管损伤右颈动脉。诱导急性心肌梗死后连续5天皮下注射G-CSF（100μg/kg/天）或生理盐水。 G-CSF治疗显着改善急性心肌梗塞大鼠的左心室功能并减少梗塞面积。 G-CSF组梗塞边缘区血管生成细胞因子mRNA的表达显着高于对照组。 G-CSF组梗死区存活心肌细胞较多。两组梗塞边界区均聚集有GFP阳性细胞；与对照组相比，G-CSF 并未增加 GFP 阳性骨髓细胞的心脏归巢。大多数 GFP 阳性细胞是 CD68 阳性（巨噬细胞）。在梗塞区域很难找到骨髓来源的心肌细胞。 G-CSF治疗抑制新内膜形成并增加受损动脉的再内皮化。 GFP 阳性细胞在受伤动脉的外膜中被发现最多。新内膜和再内皮化中的少数细胞呈 GFP 阳性。总之，给予G-CSF似乎可以有效治疗急性心肌梗死后的左心室重构，并且不会加剧血管重构。 G-CSF对心脏和血管重塑的作用可能主要通过对心脏和动脉的直接作用而发生。 (c) 2006 Elsevier B.V. 保留所有权利。
Although granulocyte colony-stimulating factor (G-CSF) has been shown to prevent cardiac remodeling after acute myocardial infarction, the mechanism and safety of G-CSF treatment acute myocardial infarction remain controversial. The purpose of the present study was to investigate in a rat model the mechanisms underlying the beneficial effect of G-CSF in acute myocardial infarction and to determine whether G-CSF treatment aggravates vascular remodeling of injured artery after acute myocardial infarction. Sprague-Dawley rats received transplanted bone marrow cells from green fluorescent protein (GFP) transgenic rats. Acute myocardial infarction was induced by ligation of the left coronary artery. After 24 h, the right carotid artery was injured with a balloon catheter. G-CSF (100 mu g/kg/day) or saline was injected subcutaneously for 5 consecutive days after induction of acute myocardial infarction. G-CSF treatment significantly improved left ventricle function and reduced infarct size in rats with acute myocardial infarction. Expression of mRNA for the angiogenic cytokines was significantly higher in the infarction border area in the G-CSF group than in the control group. The surviving cardiomyocytes in infarction area were more in the G-CSF group. GFP-positive cells were gathered in the infarction border area in both groups; G-CSF did not increase cardiac homing of GFP-positive bone marrow cells in contrast to control group. Most GFP-positive cells were CD68-positive (macrophages). It was difficult to find bone marrow-derived cardiomyocytes in the infarcted area. G-CSF treatment inhibited neointima fort-nation and increased reendothelialization of the injured artery. GFP-positive cells were identified most in the adventitia of the injured artery. A few cells in the neointima and reendothelialization were GFP positive. In conclusion, administration of G-CSF appears to be effective for treatment of left ventricular remodeling after acute myocardial infarction and does not aggravate vascular remodeling. The effect of G-CSF on cardiac and vascular remodeling may occur mainly through a direct action on the heart and arteries. (c) 2006 Elsevier B.V. All rights reserved.