The Bispecific SDF1-GPVI Fusion Protein Preserves Myocardial Function After Transient Ischemia in Mice
- 7 February 2012
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 125 (5), 685-696
- https://doi.org/10.1161/circulationaha.111.070508
Abstract
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.Keywords
This publication has 46 references indexed in Scilit:
- Disrupting the EMMPRIN (CD147)–Cyclophilin A Interaction Reduces Infarct Size and Preserves Systolic Function After Myocardial Ischemia and ReperfusionArteriosclerosis, Thrombosis, and Vascular Biology, 2011
- Implantation of Mouse Embryonic Stem Cell-Derived Cardiac Progenitor Cells Preserves Function of Infarcted Murine HeartsPLOS ONE, 2010
- Expression of stromal-cell-derived factor-1 on circulating platelets is increased in patients with acute coronary syndrome and correlates with the number of CD34+ progenitor cellsEuropean Heart Journal, 2008
- Regenerative medicine and human models of human diseaseNature, 2008
- Stromal Cell–Derived Factor-1α Is Cardioprotective After Myocardial InfarctionCirculation, 2008
- Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heartThe Journal of Experimental Medicine, 2007
- Stromal Cell–Derived Factor-1α Confers Protection Against Myocardial Ischemia/Reperfusion InjuryCirculation, 2007
- Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytesNature Medicine, 2006
- Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivoThe Journal of Experimental Medicine, 2006
- Therapeutic stem and progenitor cell transplantation for organ vascularization and regenerationNature Medicine, 2003