Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2191185 | Journal of Molecular and Cellular Cardiology | 2009 | 8 Pages |
Abstract
We have previously reported that administration of granulocyte colony-stimulating factor (G-CSF)Â +Â Flt-3 ligand (FL) or G-CSFÂ +Â stem cell factor (SCF) improves left ventricular (LV) function and halts LV remodeling at 35Â 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-CSFÂ +Â FL (group II), G-CSFÂ +Â SCF (group III), or G-CSF alone (group IV) starting 4Â h after reperfusion and were euthanized 48Â wk later. LV structure and function were assessed by serial echocardiography before and at 48Â h and 4, 8, 16, 32, and 48Â 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 4Â wk after MI; however, only in group II was this improvement sustained at 48Â 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 11Â months, and thus is likely to be permanent. In contrast, the effect of G-CSFÂ +Â 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.
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Authors
Santosh K. Sanganalmath, Adam B. Stein, Yiru Guo, Sumit Tiwari, Greg Hunt, Robert J. Vincent, Yiming Huang, Arash Rezazadeh, Suzanne T. Ildstad, Buddhadeb Dawn, Roberto Bolli,