Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction.
J Thorac Cardiovasc Surg
; 140(5): 1174-80, 2010 Nov.
Article
en En
| MEDLINE
| ID: mdl-20951261
OBJECTIVES: Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. METHODS: EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n = 48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 µg/kg of SDF-1α, 3 µg/kg of spliced SDF analog, or 6 µg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. RESULTS: EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. CONCLUSIONS: A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
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Células Madre
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Cardiotónicos
/
Movimiento Celular
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Función Ventricular Izquierda
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Células Endoteliales
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Quimiocina CXCL12
/
Infarto del Miocardio
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
J Thorac Cardiovasc Surg
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos