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Title
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Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium
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Author
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Abstract
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| BackgroundStromal 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 ResultsWe 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-4resistant 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. ConclusionsThese 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. |
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Language
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English
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Source (journal)
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Circulation : heart failure
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Publication
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2011
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ISSN
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1941-3289
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DOI
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10.1161/CIRCHEARTFAILURE.110.960302
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Volume/pages
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4
:4
(2011)
, p. 509-518
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ISI
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000292871300017
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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