Endothelial Progenitor Cells Are Rapidly Recruited to Myocardium and Mediate Protective Effect of Ischemic Preconditioning via “Imported” Nitric Oxide Synthase Activity
Background— The function of bone marrow–derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as re...
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| Published in | Circulation (New York, N.Y.) Vol. 111; no. 9; pp. 1114 - 1120 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hagerstown, MD
Lippincott Williams & Wilkins
08.03.2005
|
| Subjects | |
| Online Access | Get full text |
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| Abstract | Background—
The function of bone marrow–derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified.
Methods and Results—
We performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning.
Conclusions—
These findings provide novel insights about the role of bone marrow–derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury. |
|---|---|
| AbstractList | Background—
The function of bone marrow–derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified.
Methods and Results—
We performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning.
Conclusions—
These findings provide novel insights about the role of bone marrow–derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury. The function of bone marrow-derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified. We performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning. These findings provide novel insights about the role of bone marrow-derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury. The function of bone marrow-derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified.BACKGROUNDThe function of bone marrow-derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified.We performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning.METHODS AND RESULTSWe performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning.These findings provide novel insights about the role of bone marrow-derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury.CONCLUSIONSThese findings provide novel insights about the role of bone marrow-derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury. |
| Author | Nishimura, Hiromi Losordo, Douglas W. Iwakura, Atsushi Asahara, Takayuki Eaton, Elizabeth Ii, Masaaki Wecker, Andrea |
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The function of bone marrow–derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and... The function of bone marrow-derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity... |
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| SubjectTerms | Animals Biological and medical sciences Blood and lymphatic vessels Blood Cells - cytology Blood Cells - enzymology Blood vessels and receptors Bone Marrow Cells - cytology Bone Marrow Cells - enzymology Bone Marrow Transplantation Capillaries - pathology Cardiology. Vascular system Cell Hypoxia Cell Movement Cells, Cultured - enzymology Coronary Circulation Coronary heart disease Cytokines - physiology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endothelial Cells - cytology Endothelial Cells - enzymology Fundamental and applied biological sciences. Psychology Heart Ischemic Preconditioning, Myocardial Male Medical sciences Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Myocardial Infarction - pathology Myocardial Ischemia - physiopathology Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - prevention & control Myocardium - enzymology Myocardium - pathology Neovascularization, Physiologic Nitric Oxide - physiology Nitric Oxide Synthase - deficiency Nitric Oxide Synthase - genetics Nitric Oxide Synthase - physiology Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Phosphorylation Protein Processing, Post-Translational Radiation Chimera Stem Cells - cytology Stem Cells - enzymology Vascular Endothelial Growth Factor A - physiology Vertebrates: cardiovascular system |
| Title | Endothelial Progenitor Cells Are Rapidly Recruited to Myocardium and Mediate Protective Effect of Ischemic Preconditioning via “Imported” Nitric Oxide Synthase Activity |
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