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Tissue Eng Part A. 2010 Nov;16(11):3329-41. doi: 10.1089/ten.TEA.2009.0739. Epub 2010 Jul 23.

Secreted frizzled related protein 4 reduces fibrosis scar size and ameliorates cardiac function after ischemic injury.

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1
Foundation for Biomedical Research and Innovation TR1308, Kobe, Japan.

Abstract

Expression of the Wnt modulator secreted frizzled related protein 4 (Sfrp4) is upregulated after heart ischemic injury. We show that intramuscular administration of recombinant Sfrp4 to rat heart ischemic injury and recanalization models prevents further deterioration of cardiac function after the ischemic injury. The effect of Sfrp4 persisted for at least 20 weeks when Sfrp4 was administered in a slow release system (Sfrp4-polyhedra) to both acute and subacute ischemic models. The histology of the dissected heart showed that the cardiac wall was thicker and the area of acellular scarring was smaller in Sfrp4-treated hearts than in controls. Increased amounts of both the inactive serine 9-phosphorylated form of glycogen synthase kinase (GSK)-3β and the active form of β-catenin were observed by immunohistology 3 days after lateral anterior descendant ligation in control, but not in Sfrp4-treated hearts. All together, we show that administration of Sfrp4 interferes with canonical Wnt signaling that could mediate the formation of acellular scar and consequently contributes to the prevention of aggravation of cardiac function.

PMID:
20528676
PMCID:
PMC2965190
DOI:
10.1089/ten.TEA.2009.0739
[Indexed for MEDLINE]
Free PMC Article

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