A single dose of protease-resistant SSDF-1(S4V) exhibited greater potency for cardioprotection and improved cardiac function compared to wild-type SDF-1 in rats with ischemia/reperfusion injury.
Does a single dose of protease-resistant SSDF-1(S4V) improve cardiac function and angiogenesis in rats with experimental ischemia/reperfusion injury compared to wild-type SDF-1?
A protease-resistant form of SDF-1 (SSDF-1(S4V)) improves angiogenesis and ventricular function in a rat model of ischemia/reperfusion injury, suggesting a potential therapeutic approach for preventing heart failure post-myocardial infarction.
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. METHODS AND 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.
Kanki et al. (Tue,) conducted a other in Ischemia/reperfusion injury. SSDF-1(S4V) vs. Wild-type SDF-1 was evaluated on Cardioprotection and cardiac function. A single dose of protease-resistant SSDF-1(S4V) exhibited greater potency for cardioprotection and improved cardiac function compared to wild-type SDF-1 in rats with ischemia/reperfusion injury.