The Bispecific SDF1-GPVI Fusion Protein Preserves Myocardial Function After Transient Ischemia in Mice

Article

关键词: ENDOTHELIAL PROGENITOR CELLS;    BONE-MARROW-CELLS;    GLYCOPROTEIN VI;    FACTOR-I;    INDUCE DIFFERENTIATION;    PLATELET-ADHESION;    CD34(+) CELLS;    INFARCTION;    STEM;    FACTOR-1-ALPHA;   

DOI  :  10.1161/CIRCULATIONAHA.111.070508

来源: SCIE

【 摘 要 】

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. (Circulation. 2012;125:685-696.)

【 授权许可】

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