- 作者：Yerem Yeghiazarians ; Muhammad Khan ; Franca S. Angeli ; Yan Zhang ; Sarah Jahn ; Megha Prasad ; Rachel Mirsky ; Henry Shih ; Petros Minasi ; Andrew Boyle ; William Grossman
- 关键词：Cytokine ; acute myocardial infarction ; erythropoietin ; granulocyte colony stimulating factor
- 刊名：Journal of Cardiac Failure
- 出版年：2010
- 出版时间：August 2010
- 年：2010
- 卷：16
- 期：8
- 页码：669-678
- 全文大小：861 K
BackgroundErythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal and clinically applicable dosages of these drugs in mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of monotherapy and combination therapy post-MI.Methods and Results
Optimal doses were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1) GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was analyzed pre-MI, at 4 hours and at 28 days post-MI. Histological assessment of infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+ mobilized cells were analyzed at day 28. LV function in the control group continued to deteriorate, whereas all treatments showed stabilization. The treatment groups resulted in less scarring, increased numbers of mobilized cells to the infarct border zone (BZ), and a reduction in the number of apoptotic cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles at the BZ.
Conclusion
We have established the optimal doses for EPO and GCSF in mobilizing HSC from the bone marrow and demonstrated that therapy with these agents, either as monotherapy or combination therapy, led to improvement of cardiac function post-MI. Combination therapy does not seem to have additive benefit over monotherapy in this model.