PMID- 22223428 OWN - NLM STAT- MEDLINE DCOM- 20120413 LR - 20131121 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 125 IP - 5 DP - 2012 Feb 7 TI - The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice. PG - 685-96 LID - 10.1161/CIRCULATIONAHA.111.070508 [doi] AB - 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. FAU - Ziegler, Melanie AU - Ziegler M AD - Innere Medizin III, Eberhard Karls Universitat, Tubingen, Otfried-Muller-Strasse 10, Tubingen, Germany. FAU - Elvers, Margitta AU - Elvers M FAU - Baumer, Yvonne AU - Baumer Y FAU - Leder, Christoph AU - Leder C FAU - Ochmann, Carmen AU - Ochmann C FAU - Schonberger, Tanja AU - Schonberger T FAU - Jurgens, Tobias AU - Jurgens T FAU - Geisler, Tobias AU - Geisler T FAU - Schlosshauer, Burkhard AU - Schlosshauer B FAU - Lunov, Oleg AU - Lunov O FAU - Engelhardt, Stefan AU - Engelhardt S FAU - Simmet, Thomas AU - Simmet T FAU - Gawaz, Meinrad AU - Gawaz M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120105 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (CXCR4 protein, mouse) RN - 0 (Chemokine CXCL12) RN - 0 (Cxcl12 protein, mouse) RN - 0 (Platelet Membrane Glycoproteins) RN - 0 (Receptors, CXCR4) RN - 0 (Recombinant Fusion Proteins) RN - 0 (platelet membrane glycoprotein VI) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Bone Marrow Cells/cytology/drug effects MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - *Cell- and Tissue-Based Therapy MH - Chemokine CXCL12/metabolism/*pharmacology/therapeutic use MH - Collagen/metabolism MH - Heart/*drug effects/*physiopathology MH - Ischemic Attack, Transient/pathology/physiopathology/*therapy MH - Mice MH - Mice, Inbred C57BL MH - Models, Animal MH - Myocardial Infarction/pathology/physiopathology/*therapy MH - Myocytes, Cardiac/drug effects/pathology MH - Neovascularization, Physiologic/drug effects MH - Platelet Membrane Glycoproteins/metabolism/*pharmacology/therapeutic use MH - Protein Binding MH - Receptors, CXCR4/metabolism MH - Recombinant Fusion Proteins/*pharmacology MH - Treatment Outcome EDAT- 2012/01/10 06:00 MHDA- 2012/04/14 06:00 CRDT- 2012/01/07 06:00 PHST- 2012/01/07 06:00 [entrez] PHST- 2012/01/10 06:00 [pubmed] PHST- 2012/04/14 06:00 [medline] AID - CIRCULATIONAHA.111.070508 [pii] AID - 10.1161/CIRCULATIONAHA.111.070508 [doi] PST - ppublish SO - Circulation. 2012 Feb 7;125(5):685-96. doi: 10.1161/CIRCULATIONAHA.111.070508. Epub 2012 Jan 5.