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

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.

• Authors: Kentaro Matsushima, Takashi Suyama, Chiemi Takenaka, Naoki Nishishita, Keiko Ikeda, Yoshito Ikada, Yoshiki Sawa, Lars Martin Jakt, Hajime Mori, Shin Kawamata
• Journal: Tissue engineering. Part A (Tissue Eng Part A) Vol. 16 Issue 11 Pg. 3329-41 (Nov 2010) ISSN: 1937-335X [Electronic] United States
• PMID: 20528676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biocompatible Materials
• Cardiotonic Agents
• Proto-Oncogene Proteins
• Recombinant Proteins
• SFRP4 protein, human
• Sfrp4 protein, mouse
• Wnt Proteins
• beta Catenin

Topics

• Animals
• Biocompatible Materials (pharmacology)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Disease Models, Animal
• Drug Delivery Systems
• Fibrosis
• Heart Function Tests
• Humans
• Injections, Intramuscular
• Male
• Myocardial Ischemia (drug therapy, genetics, pathology, physiopathology)
• Proto-Oncogene Proteins (administration & dosage, genetics, metabolism, pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage, pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• Transcription, Genetic (drug effects)
• Up-Regulation (genetics)
• Wnt Proteins (metabolism)
• beta Catenin (metabolism)