Publication Date:
2008-11-16
Description:
Despite promising pre-clinical results, administration of granulocyte-colony stimulating factor (G-CSF) for improving heart function in humans after acute myocardial infarction has been disappointing. Therefore, a better understanding of the mechanism(s) of heart repair by G-CSF is urgently required. To address the potential mechanism of G-CSF, we have generated chimeric mice using G-CSF receptor knockout mice to distinguish the hematopoietic benefits of G-CSF from the direct effects of G-CSF on cardiomyocytes and blood vessels. Lethally irradiated wild-type mice were reconstituted with G-CSFR −/− bone marrow (BM) cells to generate G-CSFR BM −/− chimeras. Alternatively, lethally irradiated G-CSFR −/− mice were reconstituted with wild-type BM cells to generate G-CSFR cardiac −/− chimeras. Myocardial ischemic injury was induced by transient (60 minutes) occlusion of the left coronary artery. Mice were treated daily with saline or G-CSF for 5 days beginning 4 hours after ischemic injury. Mice were sacrificed 28 days post-injury for assessment of cardiac function and cellular repair. As previously reported in wild-type mice, G-CSFR −/− cardiac chimeras had 30–50% improved cardiac function compared with saline-treated G-CSFR −/− cardiac chimeras (ANOVA; P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink