Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 528-535 |
| Number of pages | 8 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 47 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2009 |
| Externally published | Yes |
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Keywords
- Bone marrow
- Cytokine
- Heart failure
- Myocardial repair
- Stem cell
- Ventricular remodeling
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine
Cite this
The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up. / Sanganalmath, Santosh K.; Stein, Adam B.; Guo, Yiru; Tiwari, Sumit; Hunt, Greg; Vincent, Robert J.; Huang, Yiming; Rezazadeh, Arash; Ildstad, Suzanne T.; Dawn, Buddhadeb; Bolli, Roberto.
In: Journal of Molecular and Cellular Cardiology, Vol. 47, No. 4, 10.2009, p. 528-535.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up
AU - Sanganalmath, Santosh K.
AU - Stein, Adam B.
AU - Guo, Yiru
AU - Tiwari, Sumit
AU - Hunt, Greg
AU - Vincent, Robert J.
AU - Huang, Yiming
AU - Rezazadeh, Arash
AU - Ildstad, Suzanne T.
AU - Dawn, Buddhadeb
AU - Bolli, Roberto
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Bone marrow
KW - Cytokine
KW - Heart failure
KW - Myocardial repair
KW - Stem cell
KW - Ventricular remodeling
UR - http://www.scopus.com/inward/record.url?scp=69249212271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69249212271&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2009.07.009
DO - 10.1016/j.yjmcc.2009.07.009
M3 - Article
C2 - 19616005
AN - SCOPUS:69249212271
VL - 47
SP - 528
EP - 535
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 4
ER -