The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)528-535
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume47
Issue number4
DOIs
StatePublished - Oct 2009
Externally publishedYes

Fingerprint

Granulocyte Colony-Stimulating Factor
Cytokines
Ventricular Remodeling
Stem Cell Factor
Left Ventricular Function
Myocardial Infarction
Therapeutics
Reperfusion
Coronary Occlusion
Left Ventricular Dysfunction
Echocardiography
Dilatation
flt3 ligand protein

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 journalArticle

Sanganalmath, SK, Stein, AB, Guo, Y, Tiwari, S, Hunt, G, Vincent, RJ, Huang, Y, Rezazadeh, A, Ildstad, ST, Dawn, B & Bolli, R 2009, 'The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up', Journal of Molecular and Cellular Cardiology, vol. 47, no. 4, pp. 528-535. https://doi.org/10.1016/j.yjmcc.2009.07.009
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. / The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up. In: Journal of Molecular and Cellular Cardiology. 2009 ; Vol. 47, No. 4. pp. 528-535.
@article{8f8d2b0455f24de8bb49277c73c6df46,
title = "The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up",
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.",
keywords = "Bone marrow, Cytokine, Heart failure, Myocardial repair, Stem cell, Ventricular remodeling",
author = "Sanganalmath, {Santosh K.} and Stein, {Adam B.} and Yiru Guo and Sumit Tiwari and Greg Hunt and Vincent, {Robert J.} and Yiming Huang and Arash Rezazadeh and Ildstad, {Suzanne T.} and Buddhadeb Dawn and Roberto Bolli",
year = "2009",
month = "10",
doi = "10.1016/j.yjmcc.2009.07.009",
language = "English (US)",
volume = "47",
pages = "528--535",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "4",

}

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 -