The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up.
The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up.
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梗死后细胞因子联合治疗的有益效果在长期随访中持续存在。
DOI：
10.1016/j.yjmcc.2009.07.009
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发表时间：
2009
影响因子：
5
通讯作者：
Bolli,Roberto
中科院分区：
文献类型：
--
作者：
Sanganalmath,SantoshK;Stein,AdamB;Guo,Yiru;Tiwari,Sumit;Hunt,Greg;Vincent,RobertJ;Huang,Yiming;Rezazadeh,Arash;Ildstad,SuzanneT;Dawn,Buddhadeb;Bolli,Roberto
我们之前报道过，粒细胞集落刺激因子 (G-CSF)+Flt-3 配体 (FL) 或 G-CSF+干细胞因子 (SCF) 的给药可改善左心室 (LV) 功能，并在心肌梗死 (MI) 后 35 天停止 LV 重塑。在当前的研究中，我们调查了这些有益效果是否能够长期持续——这是临床转化的一个至关重要的问题。接受 30 分钟冠状动脉闭塞然后再灌注的小鼠在再灌注后 4 小时开始接受载体（第 I 组）、G-CSF+FL（第 II 组）、G-CSF+SCF（第 III 组）或单独的 G-CSF（第 IV 组），并在 48 周后被安乐死。在 MI 之前、48 小时以及 4、8、16、32 和 48 周时通过系列超声心动图评估 LV 结构和功能。在随访过程中，第一组小鼠表现出左室功能恶化和进行性左室重塑。与 I 组相比，II 组和 III 组在 MI 后 4 周时 LV EF 均有所改善；然而，只有第二组的这种改善持续到了 48 周。与第 I 组相比，第 II 组也是唯一一组梗死壁增厚分数的减少、左心室扩张和左心室质量增加有所减弱。我们得出的结论是，G-CSF+FL 对梗死后左心室功能障碍和重塑的有益作用可持续至少 11 个月，因此可能是永久性的。相比之下，G-CSF+SCF的效果在最初几周后就无法持续，单独使用G-CSF是无效的。据我们所知，这是第一个关于细胞因子在梗死后左室重塑中的长期研究。结果揭示了迄今为止未知的细胞因子的差异作用，并具有重要的翻译意义。
We have previously reported that administration of granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL) or G-CSF+stem cell factor (SCF) improves left ventricular (LV) function and halts LV remodeling at 35 d after myocardial infarction (MI). In the current study, we investigated whether these beneficial effects are sustained in the long term — an issue of fundamental importance for clinical translation. Mice undergoing a 30-min coronary occlusion followed by reperfusion received vehicle (group I), G-CSF+FL (group II), G-CSF+SCF (group III), or G-CSF alone (group IV) starting 4 h after reperfusion and were euthanized 48 wk later. LV structure and function were assessed by serial echocardiography before and at 48 h and 4, 8, 16, 32, and 48 wk after MI. During follow-up, mice in group I exhibited worsening of LV function and progressive LV remodeling. Compared with group I, both groups II and III exhibited improved LV EF at 4 wk after MI; however, only in group II was this improvement sustained at 48 wk. Group II was also the only group in which the decrease in infarct wall thickening fraction, the LV dilatation, and the increase in LV mass were attenuated vs. group I. We conclude that the beneficial effect of G-CSF+FL on postinfarction LV dysfunction and remodeling is sustained for at least 11 months, and thus is likely to be permanent. In contrast, the effect of G-CSF+SCF was not sustained beyond the first few weeks, and G-CSF alone is ineffective. To our knowledge, this is the first long-term study of cytokines in postinfarction LV remodeling. The results reveal heretofore unknown differential actions of cytokines and have important translational implications.