Circulation. 2004;110:3300-3305
Published online before print November 8, 2004, doi: 10.1161/01.CIR.0000147780.30124.CF
Published online before print November 8, 2004, doi: 10.1161/01.CIR.0000147780.30124.CF
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(Circulation. 2004;110:3300-3305.)
© 2004 American Heart Association, Inc.
Coronary Heart Disease |
Stromal Cell–Derived Factor-1
Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury
From the Departments of Cardiology (J.D.A., Y.H., D.L., R.H., F.J.G.) and Laboratory Medicine (D.S.K.), Yale University Medical School, New Haven, Conn.
Correspondence to Frank J. Giordano, BCMM 439, 295 Congress Ave, New Haven, CT 06510. E-mail frank.giordano{at}yale.edu
Received April 24, 2004; revision received June 21, 2004; accepted August 3, 2004.
Background— After myocardial infarction (MI), bone marrow–derived cells (BMDCs) are found within the myocardium. The mechanisms determining BMDC recruitment to the heart remain unclear. We investigated the role of stromal cell–derived factor-1
(SDF-1) in this process.
Methods and Results— MI produced in mice by coronary ligation induced SDF-1 mRNA and protein expression in the infarct and border zone and decreased serum SDF-1 levels. By quantitative polymerase chain reaction, 48 hours after intravenous infusion of donor-lineage BMDCs, there were 80.5±15.6% more BDMCs in infarcted hearts compared with sham-operated controls (P<0.01). Administration of AMD3100, which specifically blocks binding of SDF-1 to its endogenous receptor CXCR4, diminished BMDC recruitment after MI by 64.2±5.5% (P<0.05), strongly suggesting a requirement for SDF-1 in BMDC recruitment to the infarcted heart. Forced expression of SDF-1 in the heart by adenoviral gene delivery 48 hours after MI doubled BMDC recruitment over MI alone (P<0.001) but did not enhance recruitment in the absence of MI, suggesting that SDF-1 can augment, but is not singularly sufficient for, BDMC recruitment to the heart. Gene expression analysis after MI revealed increased levels of several genes in addition to SDF-1, including those for vascular endothelial growth factor, matrix metalloproteinase-9, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, which might act in concert with SDF-1 to recruit BMDCs to the injured heart.
Conclusion— SDF-1/CXCR4 interactions play a crucial role in the recruitment of BMDCs to the heart after MI and can further increase homing in the presence, but not in the absence, of injury.
Key Words: cell adhesion molecules • cells • growth factors • myocardial infarction
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A. Zernecke, A. Schober, I. Bot, P. von Hundelshausen, E. A. Liehn, B. Mopps, M. Mericskay, P. Gierschik, E. A. Biessen, and C. Weber SDF-1{alpha}/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells Circ. Res., April 15, 2005; 96(7): 784 - 791. [Abstract] [Full Text] [PDF]
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