title: Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium.
abstract: BACKGROUND
  Stromal cell-derived factor-1 (SDF-1) is a chemoattractant of stem/progenitor cells, and several studies have shown that SDF-1 may improve ventricular function after infarction. SDF-1 is cleaved by proteases including matrix metalloproteinase-2 (MMP-2) and CD26/dipeptidylpeptidase-4 (DPP-4), which are activated in injured tissues.
  
  
  RESULTS
  We investigated the biodistribution and functional roles of SDF-1 in experimental ischemia/reperfusion injury in rats. Radiolabeled SDF-1 given by intracoronary injection was selectively concentrated in ischemic myocardium. The enhanced uptake of SDF-1 in ischemic myocardium was not mediated by its receptor, CXCR4. Mass spectrometry and Western analyses showed that SDF-1 was cleaved by DPP-4 in plasma and myocardium, whereas a bioengineered MMP-2/DPP-4-resistant form of SDF-1, SSDF-1(S4V), was highly stable. A single dose of SSDF-1(S4V) exhibited greater potency for cardioprotection than wild-type SDF-1. SSDF-1(S4V) improved cardiac function in rats even after a 3-hour ischemic period.
  
  
  CONCLUSIONS
  These results show that a single dose of protease-resistant SSDF-1(S4V) after myocardial infarction leads to dramatic improvement in angiogenesis and ventricular function even 3 hours after the onset of ischemia, revealing a simple, clinically feasible approach to prevention of heart failure.
authors: Harvard Stem Cell Institute, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
authors: Sachiko
authors: S
authors: Kanki
authors: Vincent F M
authors: VF
authors: Segers
authors: Weitao
authors: W
authors: Wu
authors: Rahul
authors: R
authors: Kakkar
authors: Joseph
authors: J
authors: Gannon
authors: Stanislas U
authors: SU
authors: Sys
authors: Anthony
authors: A
authors: Sandrasagra
authors: Richard T
authors: RT
authors: Lee