- 作者：Jonathan M. Hill ; Mushabbar A. Syed ; Andrew E. Arai ; Tiffany M. Powell ; Jonathan D. Paul ; Gloria Zalos ; Elizabeth J. Read ; Hanh M. Khuu ; Susan F. Leitman ; McDonald Horne ; Gyorgy Csako ; Cynthia E. Dunb
- 刊名：Journal of the American College of Cardiology
- 出版年：2005
- 出版时间：1 November 2005
- 年：2005
- 卷：46
- 期：9
- 页码：1643-1648
- 全文大小：169 K
Objectives
Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia.Background
Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects.
Methods
Granulocyte colony-stimulating factor (G-CSF), 10 μg/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging.
Results
Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 ± 0.2 μl to 52.4 ± 10.4 μl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 ± 12.6 μl, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 ± 1.3 mg/l to 8.6 ± 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non–ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 ± 2.1 to 28.3 ± 1.9, p = 0.196) or segments with abnormal perfusion (7.6 ± 1.1 to 7.7 ± 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 ± 0.6 to 6.1 ± 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline.
Conclusions
Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.