Table 1

Experimental Studies Examining the Effects of SDF-1/CXCR4 Signaling in Myocardial Infarction

Strategy UsedModelMain FindingsRef. #
Gain-of-function studies
 Intramyocardial SDF-1 injection (300 ng) at the time of occlusionMouse (NR)SDF-1 therapy improved systolic function, enhancing cardiomyocyte survival and increasing infarct angiogenesis.(6)
 Intramyocardial SDF-1 injection (1 μg) during occlusionMouse (NR)SDF-1 therapy improved systolic function, reduced infarct size, and enhanced angiogenesis.(9)
 Intraventricular SDF-1 injection (35 μg/kg/min) for 5 min before occlusionMouse (R)SDF-1 treatment reduced infarct size.(10)
 Intramyocardial injection of a protease-resistant SDF-1Rat (NR)SDF-1 therapy improved systolic function, inducing recruitment of CXCR4+ progenitor cells and increasing angiogenesis.(8)
 Systemic infusion of SDF-1–overexpressing MSCs 1 day post-infarctionRat (NR)SDF-1–expressing MSCs increased angiogenesis and enhanced cardiomyocyte survival.(7)
 Systemic infusion of CXCR4+ MSCs 3 days post-infarctionRat (NR)CXCR4-overexpressing MSCs had attenuated cardiac dysfunction associated with angiogenesis and myogenesis.(16)
 Transplantation of SDF-1–overexpressing fibroblasts 8 weeks after infarctionRat (NR)SDF-1–expressing fibroblasts induced homing of filgastrim-mobilized CD117+ stem cells into the myocardium and improved cardiac function.(4)
 Adenovirus-mediated CXCR4 gene therapy 1 week before coronary occlusionRat (R)CXCR4 overexpression accentuated myocardial inflammation, increased cardiomyocyte apoptosis, and worsened cardiac dysfunction.(11)
 Adenovirus-mediated SDF-1 overexpression 4 h post-infarction in animals receiving bone marrow-derived cellsMouse (NR)SDF-1 overexpression increased recruitment of bone marrow–derived cells in the infarct.(17)
Pharmacologic inhibition studies
 Continuous subcutaneous infusion with the CXCR4 inhibitor AMD3100 for 20 days after occlusionMouse (NR)Inhibition of the SDF-1/CXCR4 axis accentuated dysfunction and adverse remodeling.(12)
 Intraperitoneal and oral treatment with AMD3100Rat (NR)Inhibition of SDF-1/CXCR4 reduced infarct size and improved ventricular function.(13)
  a. Single-dose AMD3100 injection after the onset of infarction;   b. continuous AMD3100 infusionMouseAcute CXCR4 antagonism improved survival and reduced cardiac remodeling, increasing mobilization and recruitment of EPCs. In contrast, long-term CXCR4 inhibition accentuated adverse remodeling and impaired EPC incorporation in the infarct border zone.(14)
Genetic loss-of-function studies
 Mice with congenital and conditional deletion of cardiomyocyte CXCR4 underwent infarction protocolsMouse (NR)Disrupted cardiomyocyte CXCR4 signaling did not affect cardiac repair and remodeling.(15)
 CXCR4+/− mice underwent infarction protocolsMouse (NR)Attenuated CXCR4 signaling was associated with reduced basal coronary flow. After infarction, CXCR4+/− mice had reduced angiogenesis and enhanced inflammatory activity. The severity of post-infarction systolic dysfunction was not affected by reduced CXCR4 signaling.(5)

EPC = endothelial progenitor cell; MSC = mesenchymal stem cell; NR = nonreperfused infarction model; R = reperfused infarction model; SDF = stromal cell–derived factor.