Macrophage colony-stimulating factor treatment after myocardial infarction attenuates left ventricular dysfunction by accelerating infarct repair.
Macrophage colony-stimulating factor treatment after myocardial infarction attenuates left ventricular dysfunction by accelerating infarct repair.
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DOI：
10.1016/j.jacc.2005.09.037
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发表时间：
2006-02
影响因子：
24
通讯作者：
T. Yano;T. Miura;P. Whittaker;T. Miki;J. Sakamoto;Yuichi Nakamura;Y. Ichikawa;Y. Ikeda;Hironori Kobayashi;K. Ohori;K. Shimamoto
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文献类型：
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作者：
T. Yano;T. Miura;P. Whittaker;T. Miki;J. Sakamoto;Yuichi Nakamura;Y. Ichikawa;Y. Ikeda;Hironori Kobayashi;K. Ohori;K. Shimamoto
目的探讨巨噬细胞集落刺激因子（M-CSF）和粒细胞集落刺激因子（G-CSF）治疗对心肌梗死（MI）后修复过程和心室功能的影响。M-CSF和G-CSF对参与伤口修复的细胞有多种潜在影响。方法采用冠脉闭塞再灌注45 min和90 min的方法，分别注射M-CSF （106IU/kg/d）和G-CSF (50 μg/kg/d)，连续5 d诱导心肌梗死。我们检查组织学和信使核糖核酸（mRNA），并使用导尿管原位评估左心室功能。结果心肌梗死后5 d， M-CSF增加了ed -1阳性细胞的数量，增加了梗死内转化生长因子-β-1、胶原I和胶原纤维的mRNA水平。心肌缺血45 min后第14天左心室收缩末期弹性（Ees）降低（1191±87 mm Hg/ml vs. 1812±150 mm Hg/ml），等容松弛时间常数（τ）（11.9±0.9 ms vs. 8.5±0.4 ms）和左心室舒张末期容积（LVEDV）（0.225±0.014 ml vs. 0.172±0.011 ml）均高于假手术大鼠。心肌梗死后的这些变化被M-CSF减弱（Ees = 1,650±146,τ = 9.7±0.7,LVEDV = 0.199±0.012），而G-CSF则没有。M-CSF对Ees的有益作用也在缺血90分钟后心肌梗死的心脏中被检测到。心肌梗死14天后，M-CSF增加了梗死区胶原含量，减少了薄胶原纤维的比例。Ees与梗死区胶原含量显著相关。然而，M-CSF和G-CSF都不能改变梗死面积。结论M-CSF治疗可通过加速梗死修复减轻心肌梗死后左心室功能的恶化。
ObjectivesWe aimed to determine the effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) treatment on both the repair process and ventricular function after myocardial infarction (MI).BackgroundThe M-CSF and G-CSF have multiple potential effects on cells involved in wound repair.MethodsMyocardial infarction was induced by 45- or 90-min coronary occlusion and reperfusion in rats with or without subsequent injection of M-CSF (106IU/kg/day) or G-CSF (50 μg/kg/day) for five days. We examined histology and messenger ribonucleic acid (mRNA), and assessed left ventricular function in situ using a conductance catheter.ResultsFive days after MI, M-CSF increased the number of ED-1–positive cells, mRNA levels of transforming growth factor-β-1, collagen I and III, and collagen fibers within the infarct. Fourteen days after MI, induced by 45-min ischemia, left ventricular end-systolic elastance (Ees) was reduced (1,191 ± 87 mm Hg/ml vs. 1,812 ± 150 mm Hg/ml) and both isovolumic relaxation time constant (τ) (11.9 ± 0.9 ms vs. 8.5 ± 0.4 ms) and left ventricular end-diastolic volume (LVEDV) (0.225 ± 0.014 ml vs. 0.172 ± 0.011 ml) increased versus sham-operated rats. These alterations after MI were attenuated by M-CSF (Ees = 1,650 ± 146, τ = 9.7 ± 0.7, LVEDV = 0.199 ± 0.012) but not by G-CSF. This beneficial effect of M-CSF on Ees was also detected in hearts with MI induced by 90-min ischemia. Furthermore, M-CSF increased collagen content within infarcts and reduced the proportion of thin collagen fibers 14 days after MI. The Ees significantly correlated with infarct collagen content. Nevertheless, neither M-CSF nor G-CSF modified infarct size.ConclusionsThe M-CSF treatment attenuates deterioration of left ventricular function after MI by accelerating infarct repair.