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Downregulation of the CXC chemokine receptor 4/stromal cell-derived factor 1 pathway enhances myocardial neovascularization, cardiomyocyte survival, and functional recovery after myocardial infarction.
J Thorac Cardiovasc Surg. 2011 Sep; 142(3):687-96, 696.e1-2.JT

Abstract

OBJECTIVES

Although adequate numbers of hematopoietic progenitor cells reside in the human bone marrow, the extent of endogenous neovascularization after myocardial infarction remains insufficient. The aim of this study was to identify the role of the CXC chemokine receptor 4/stromal cell-derived factor 1 axis in the mobilization and homing of hematopoietic progenitor cells in the ischemic heart.

METHODS

Human bone marrow-derived hematopoietic progenitor cells or saline were injected systemically into athymic nude rats 48 hours after myocardial infarction. Myocardial and bone marrow expression of stromal cell-derived factor 1 and chemotaxis of hematopoietic progenitor cells were measured in vitro in the presence or absence of stromal cell-derived factor 1. The role of the CXC chemokine receptor 4/stromal cell-derived factor 1 axis was investigated by means of antibody blockade or systemic administration of granulocyte colony-stimulating factor. Morphologic analysis included measurement of the infarct area, capillary density, and apoptosis, whereas left ventricular function was measured by means of echocardiographic analysis.

RESULTS

Expression of postinfarct stromal cell-derived factor 1 was increased by 67% in the bone marrow and decreased by 43% in myocardium. Disruption of bone marrow stromal cell-derived factor 1/CXC chemokine receptor 4 interactions by antibody blockade resulted in a redirection of human hematopoietic progenitor cells from the bone marrow to the ischemic heart and augmented neovascularization and cardiomyocyte survival. Similarly, systemic administration of granulocyte colony-stimulating factor to block CXC chemokine receptor 4/stromal cell-derived factor 1 interaction resulted in increased mobilization and homing of hematopoietic progenitor cells to the ischemic heart, which translated to augmented myocardial neovascularization, prevention of apoptosis, and improved cardiac function.

CONCLUSIONS

Bone marrow stromal cell-derived factor 1 upregulation after myocardial ischemia prevents mobilization of endogenous hematopoietic progenitor cells. We provide evidence that disruption of stromal cell-derived factor 1/CXC chemokine receptor 4 interactions allows redirection of hematopoietic progenitor cells to ischemic myocardium and enhances recovery of left ventricular function.

Authors+Show Affiliations

Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria. Nikolaos.bonaros@i-med.ac.atNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21388641

Citation

Bonaros, Nikolaos, et al. "Downregulation of the CXC Chemokine Receptor 4/stromal Cell-derived Factor 1 Pathway Enhances Myocardial Neovascularization, Cardiomyocyte Survival, and Functional Recovery After Myocardial Infarction." The Journal of Thoracic and Cardiovascular Surgery, vol. 142, no. 3, 2011, pp. 687-96, 696.e1-2.
Bonaros N, Sondermeijer H, Wiedemann D, et al. Downregulation of the CXC chemokine receptor 4/stromal cell-derived factor 1 pathway enhances myocardial neovascularization, cardiomyocyte survival, and functional recovery after myocardial infarction. J Thorac Cardiovasc Surg. 2011;142(3):687-96, 696.e1-2.
Bonaros, N., Sondermeijer, H., Wiedemann, D., Schlechta, B., Schachner, T., Schuster, M., Seki, T., Martens, T. P., Itescu, S., & Kocher, A. A. (2011). Downregulation of the CXC chemokine receptor 4/stromal cell-derived factor 1 pathway enhances myocardial neovascularization, cardiomyocyte survival, and functional recovery after myocardial infarction. The Journal of Thoracic and Cardiovascular Surgery, 142(3), 687-96, e1-2. https://doi.org/10.1016/j.jtcvs.2011.01.014
Bonaros N, et al. Downregulation of the CXC Chemokine Receptor 4/stromal Cell-derived Factor 1 Pathway Enhances Myocardial Neovascularization, Cardiomyocyte Survival, and Functional Recovery After Myocardial Infarction. J Thorac Cardiovasc Surg. 2011;142(3):687-96, 696.e1-2. PubMed PMID: 21388641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of the CXC chemokine receptor 4/stromal cell-derived factor 1 pathway enhances myocardial neovascularization, cardiomyocyte survival, and functional recovery after myocardial infarction. AU - Bonaros,Nikolaos, AU - Sondermeijer,Hugo, AU - Wiedemann,Dominik, AU - Schlechta,Bernhard, AU - Schachner,Thomas, AU - Schuster,Michael, AU - Seki,Tetsunori, AU - Martens,Timothy P, AU - Itescu,Silviu, AU - Kocher,Alfred A, Y1 - 2011/03/08/ PY - 2010/09/27/received PY - 2010/12/15/revised PY - 2011/01/07/accepted PY - 2011/3/11/entrez PY - 2011/3/11/pubmed PY - 2011/10/14/medline SP - 687-96, 696.e1-2 JF - The Journal of thoracic and cardiovascular surgery JO - J Thorac Cardiovasc Surg VL - 142 IS - 3 N2 - OBJECTIVES: Although adequate numbers of hematopoietic progenitor cells reside in the human bone marrow, the extent of endogenous neovascularization after myocardial infarction remains insufficient. The aim of this study was to identify the role of the CXC chemokine receptor 4/stromal cell-derived factor 1 axis in the mobilization and homing of hematopoietic progenitor cells in the ischemic heart. METHODS: Human bone marrow-derived hematopoietic progenitor cells or saline were injected systemically into athymic nude rats 48 hours after myocardial infarction. Myocardial and bone marrow expression of stromal cell-derived factor 1 and chemotaxis of hematopoietic progenitor cells were measured in vitro in the presence or absence of stromal cell-derived factor 1. The role of the CXC chemokine receptor 4/stromal cell-derived factor 1 axis was investigated by means of antibody blockade or systemic administration of granulocyte colony-stimulating factor. Morphologic analysis included measurement of the infarct area, capillary density, and apoptosis, whereas left ventricular function was measured by means of echocardiographic analysis. RESULTS: Expression of postinfarct stromal cell-derived factor 1 was increased by 67% in the bone marrow and decreased by 43% in myocardium. Disruption of bone marrow stromal cell-derived factor 1/CXC chemokine receptor 4 interactions by antibody blockade resulted in a redirection of human hematopoietic progenitor cells from the bone marrow to the ischemic heart and augmented neovascularization and cardiomyocyte survival. Similarly, systemic administration of granulocyte colony-stimulating factor to block CXC chemokine receptor 4/stromal cell-derived factor 1 interaction resulted in increased mobilization and homing of hematopoietic progenitor cells to the ischemic heart, which translated to augmented myocardial neovascularization, prevention of apoptosis, and improved cardiac function. CONCLUSIONS: Bone marrow stromal cell-derived factor 1 upregulation after myocardial ischemia prevents mobilization of endogenous hematopoietic progenitor cells. We provide evidence that disruption of stromal cell-derived factor 1/CXC chemokine receptor 4 interactions allows redirection of hematopoietic progenitor cells to ischemic myocardium and enhances recovery of left ventricular function. SN - 1097-685X UR - https://www.unboundmedicine.com/medline/citation/21388641/Downregulation_of_the_CXC_chemokine_receptor_4/stromal_cell_derived_factor_1_pathway_enhances_myocardial_neovascularization_cardiomyocyte_survival_and_functional_recovery_after_myocardial_infarction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-5223(11)00042-0 DB - PRIME DP - Unbound Medicine ER -