Yano Toshiyuki, Miura Tetsuji, Whittaker Peter, Miki Takayuki, Sakamoto Jun, Nakamura Yuichi, Ichikawa Yoshihiko, Ikeda Yoshihiro, Kobayashi Hironori, Ohori Katsuhiko, Shimamoto Kazuaki
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Am Coll Cardiol. 2006 Feb 7;47(3):626-34. doi: 10.1016/j.jacc.2005.09.037. Epub 2006 Jan 20.
We 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).
The M-CSF and G-CSF have multiple potential effects on cells involved in wound repair.
Myocardial infarction was induced by 45- or 90-min coronary occlusion and reperfusion in rats with or without subsequent injection of M-CSF (10(6) IU/kg/day) or G-CSF (50 microg/kg/day) for five days. We examined histology and messenger ribonucleic acid (mRNA), and assessed left ventricular function in situ using a conductance catheter.
Five days after MI, M-CSF increased the number of ED-1-positive cells, mRNA levels of transforming growth factor-beta-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 (tau) (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, tau = 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.
The M-CSF treatment attenuates deterioration of left ventricular function after MI by accelerating infarct repair.
我们旨在确定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具有多种潜在作用。
通过45或90分钟的冠状动脉闭塞和再灌注在大鼠中诱导心肌梗死，随后对有或没有后续注射M-CSF（10⁶ IU/kg/天）或G-CSF（50微克/千克/天）的大鼠进行为期五天的注射。我们检查了组织学和信使核糖核酸（mRNA），并使用电导导管原位评估左心室功能。
心肌梗死后五天，M-CSF增加了梗死区内ED-1阳性细胞的数量、转化生长因子-β1、I型和III型胶原蛋白的mRNA水平以及胶原纤维。在由45分钟缺血诱导的心肌梗死后十四天，左心室收缩末期弹性（Ees）降低（1191±87 mmHg/ml对1812±150 mmHg/ml），等容舒张时间常数（tau）（11.9±0.9 ms对8.5±0.4 ms）和左心室舒张末期容积（LVEDV）（0.225±0.014 ml对0.172±0.011 ml）与假手术大鼠相比增加。心肌梗死后的这些改变被M-CSF减轻（Ees = 1650±146，tau = 9.7±0.7，LVEDV = 0.199±0.012），但未被G-CSF减轻。在由90分钟缺血诱导的心肌梗死的心脏中也检测到M-CSF对Ees的这种有益作用。此外，M-CSF增加了心肌梗死后14天梗死区内的胶原蛋白含量并降低了细胶原纤维的比例。Ees与梗死区胶原蛋白含量显著相关。然而，M-CSF和G-CSF均未改变梗死面积。
M-CSF治疗通过加速梗死修复减轻心肌梗死后左心室功能的恶化。
