TY - JOUR

T1 - The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice.

AU - Ziegler, Melanie

AU - Elvers, Margitta

AU - Baumer, Yvonne

AU - Leder, Christoph

AU - Ochmann, Carmen

AU - Schönberger, Tanja

AU - Jürgens, Tobias

AU - Geisler, Tobias

AU - Schlosshauer, Burkhard

AU - Lunov, Oleg

AU - Engelhardt, Stefan

AU - Simmet, Thomas

AU - Gawaz, Meinrad

PY - 2012/2/7

Y1 - 2012/2/7

N2 - 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.

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.

KW - Health sciences

KW - GPVI

KW - myocardial infarction

KW - cells

KW - SDF-1

KW - tissue repair

KW - Sustainability Science

UR - http://www.scopus.com/inward/record.url?scp=84857048486&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.111.070508

DO - 10.1161/CIRCULATIONAHA.111.070508

M3 - Journal articles

VL - 125

SP - 685

EP - 696

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 5

ER -