The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice.

Research output: Journal contributionsJournal articlesResearchpeer-review

Authors

  • Melanie Ziegler
  • Margitta Elvers
  • Yvonne Baumer
  • Christoph Leder
  • Carmen Ochmann
  • Tanja Schönberger
  • Tobias Jürgens
  • Tobias Geisler
  • Burkhard Schlosshauer
  • Oleg Lunov
  • Stefan Engelhardt
  • Thomas Simmet
  • Meinrad Gawaz

Background-CXCR4-positive bone marrow cells (BMCs) are critically involved in cardiac repair mechanisms contributing to preserved cardiac function. Stromal cell-derived factor-1 (SDF-1) is the most prominent BMC homing factor known to augment BMC engraftment, which is a limiting step of stem cell-based therapy. After myocardial infarction, SDF-1 expression is rapidly upregulated and promotes myocardial repair. Methods and Results-We have established a bifunctional protein consisting of an SDF-1 domain and a glycoprotein VI (GPVI) domain with high binding affinity to the SDF-1 receptor CXCR4 and extracellular matrix proteins that become exposed after tissue injury. SDF1-GPVI triggers chemotaxis of CXCR4-positive cells, preserves cell survival, enhances endothelial differentiation of BMCs in vitro, and reveals proangiogenic effects in ovo. In a mouse model of myocardial infarction, administration of the bifunctional protein leads to enhanced recruitment of BMCs, increases capillary density, reduces infarct size, and preserves cardiac function. Conclusions-These results indicate that administration of SDF1-GPVI may be a promising strategy to treat myocardial infarction to promote myocardial repair and to preserve cardiac function.

Original languageEnglish
JournalCirculation
Volume125
Issue number5
Pages (from-to)685-696
Number of pages12
ISSN0009-7322
DOIs
Publication statusPublished - 07.02.2012