The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice.
Publikation: Beiträge in Zeitschriften › Zeitschriftenaufsätze › Forschung › begutachtet
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The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice. / Ziegler, Melanie; Elvers, Margitta; Baumer, Yvonne et al.
in: Circulation, Jahrgang 125, Nr. 5, 07.02.2012, S. 685-696.Publikation: Beiträge in Zeitschriften › Zeitschriftenaufsätze › Forschung › begutachtet
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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 -