Stromal Cell–Derived Factor-1α Is Cardioprotective After Myocardial Infarction
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Cardiotonic Agents
Myocardium
Myocardial Infarction
Myocardial Ischemia
Neovascularization, Physiologic
Apoptosis
Chemokine CXCL12
Ventricular Function, Left
3. Good health
Mice, Inbred C57BL
Mice
03 medical and health sciences
0302 clinical medicine
Echocardiography
Animals
Regeneration
Phosphorylation
Proto-Oncogene Proteins c-akt
DOI:
10.1161/circulationaha.107.694992
Publication Date:
2008-04-22T02:44:30Z
AUTHORS (8)
ABSTRACT
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-1α (SDF-1α), 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-1α demonstrated significantly decreased scar formation than control mice.
Conclusion—
These findings suggest that SDF-1α may serve a tissue-protective and regenerative role for solid organs suffering a hypoxic insult.
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