Published Online
on April 21, 2008

A more recent version of this article appeared on April 29, 2008

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Submitted on February 5, 2007
Accepted on January 18, 2008

Stromal Cell–Derived Factor-1 Is Cardioprotective After Myocardial Infarction

Ankur Saxena PhD, Jason E. Fish PhD, Michael D. White BS, Sangho Yu BS, James W.P. Smyth PhD, Robin M. Shaw MD, PhD, J. Michael DiMaio MD, and Deepak Srivastava MD^*

From the Gladstone Institute of Cardiovascular Disease and Departments of Pediatrics and Biochemistry and Biophysics (D.S., J.E.F., S.Y.) and the Cardiovascular Research Institute and the Department of Medicine (J.W.P.S., R.M.S.), University of California, San Francisco; and Departments of Pediatrics and Molecular Biology (A.S.) and Department of Cardiovascular and Thoracic Surgery (M.D.W., J.M.D.), University of Texas Southwestern Medical Center, Dallas.

^* To whom correspondence should be addressed. E-mail: dsrivastava{at}gladstone.ucsf.edu.

Background—Heart disease is a leading cause of mortality throughout the world. Tissue damage from vascular occlusive events results in the replacement of contractile myocardium by nonfunctional scar tissue. The potential of new technologies to regenerate damaged myocardium is significant, although cell-based therapies must overcome several technical barriers. One possible cell-independent alternative is the direct administration of small proteins to damaged myocardium.

Methods and Results—Here we show that the secreted signaling protein stromal cell–derived factor-1 (SDF-1), which activates the cell-survival factor protein kinase B (PKB/Akt) via the G protein–coupled receptor CXCR4, protected tissue after an acute ischemic event in mice and activated Akt within endothelial cells and myocytes of the heart. Significantly better cardiac function than in control mice was evident as early as 24 hours after infarction as well as at 3, 14, and 28 days after infarction. Prolonged survival of hypoxic myocardium was followed by an increase in levels of vascular endothelial growth factor protein and neoangiogenesis. Consistent with improved cardiac function, mice exposed to SDF-1 demonstrated significantly decreased scar formation than control mice.

Conclusion—These findings suggest that SDF-1 may serve a tissue-protective and regenerative role for solid organs suffering a hypoxic insult.

Key words: angiogenesis • apoptosis • ischemia • myocardial infarction

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Clinical Summaries
Circulation 2008 117: 2169. [Extract] [Full Text]

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