Postinfarction cardiac remodeling normally proceeds in granulocyte colony-stimulating factor knockout mice.
Postinfarction cardiac remodeling normally proceeds in granulocyte colony-stimulating factor knockout mice.
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梗死后心脏重塑通常在粒细胞集落刺激因子敲除小鼠中进行。
DOI：
10.1016/j.ajpath.2015.03.018
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发表时间：
2015
期刊：
影响因子：
6
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Morishita K;Takemura G;et al.
据报道，粒细胞集落刺激因子（G-CSF）治疗可减轻梗死后心脏重构和功能障碍。我们在此研究了G-CSF敲除（G-CSF- ko）对小鼠心肌梗死后重构过程的影响。出乎意料的是，结扎后24小时两组的急性梗死面积相似。在慢性期（4周后），两组在左心室尺寸、左心室功能或组织学表现（包括血管密度）方面没有差异。此外，与野生型小鼠相比，G-CSF-KO小鼠心脏中血管内皮生长因子（VEGF）的表达明显上调。微阵列未检测到VEGF mRNA的上调，而G-CSF显著降低了小鼠心肌中VEGF的表达，表明G-CSF转录后下调了VEGF的表达。当G-CSF-KO小鼠接受抗vegf抗体（贝伐单抗）治疗时，心脏重构明显加重，梗死壁变薄，包括血管在内的细胞成分减少。在梗死后4天，贝伐单抗治疗的心脏肉芽组织中，血管发育稀少，细胞增殖减少，细胞凋亡增加，这可能导致梗死壁变薄，从而导致慢性期壁应力和心脏重塑的增加。总之，在梗死后的心脏中，VEGF的过表达可能通过保存细胞成分（包括血管）来补偿G-CSF的缺陷。
Treatment with granulocyte colony-stimulating factor (G-CSF) reportedly mitigates postinfarction cardiac remodeling and dysfunction. We herein examined the effects of G-CSF knockout (G-CSF-KO) on the postinfarction remodeling process in the hearts of mice. Unexpectedly, the acute infarct size 24 hours after ligation was similar in the two groups. At the chronic stage (4 weeks later), there was no difference in the left ventricular dimension, left ventricular function, or histological findings, including vascular density, between the two groups. In addition, expression of vascular endothelial growth factor (VEGF) was markedly up-regulated in hearts from G-CSF-KO mice, compared with wild-type mice. Microarray failed in detecting up-regulation of VEGF mRNA, whereas G-CSF administration significantly decreased myocardial VEGF expression in mice, indicating that G-CSF post-transcriptionally down-regulates VEGF expression. When G-CSF-KO mice were treated with an anti-VEGF antibody (bevacizumab), cardiac remodeling was significantly aggravated, with thinning of the infarct wall and reduction of the cellular component, including blood vessels. In the granulation tissue of bevacizumab-treated hearts 4 days after infarction, vascular development was scarce, with reduced cell proliferation and increased apoptosis, which likely contributed to the infarct wall thinning and the resultant increase in wall stress and cardiac remodeling at the chronic stage. In conclusion, overexpression of VEGF may compensate for the G-CSF deficit through preservation of cellular components, including blood vessels, in the postinfarction heart.