Abstract 13483: The Cleavage Fragments of Complement Component 3 (C3) are Required for Efficient Mobilization of Hematopoietic and Cardiac Stem/Progenitor Cells in Response to Acute Myocardial Infarction (mi).
In response to myocardial infarction (MI) the number of hematopoietic, endothelial, cardiac and stromal/progenitor cells and pluripotent Very Small Embryonic Like stem cells circulating in peripheral blood (PB) increase. Since the bone marrow is a source of tissue committed and pluripotent stem cells in addition to hematopoietic stem cells, these cells could be mobilized into PB after MI directly from the bone marrow (BM) microenvironment. The complement system has been reported to play a role in the regulation of mobilization of BM-residing stem/progenitor cells in response to G-CSF. Since the complement system is also activated after MI, we postulated that the complement system regulates mobilization of BM stem/progenitor cells in response to MI. In our studies we employed a murine model of myocardial infarction (chronic coronary artery ligation). We noticed that mobilization of hematopoietic stem/progenitor cells after MI in C3 deficient mice (C3KO) was impaired where the number of circulating clonogenic progenitors for CFU-GMs and BFU-Es and the number of circulating SKL and SKL CD34- evaluated by Flow Cytometry were significantly decreased compared to WT mice. Furthermore, C3KOmice had lower numbers of circulating cardiac stem/progenitor cells as indicated by number of Lin-CD45-c-kit+ cells (by Flow Cytometry) and frequency Nkx2.5 and GATA-4 positive cells (by real time PCR). Next, decreased circulating stem/progenitor cells of hematopoietic and cardiac lineage correlated with decreased myocardial function analyzed by echocardiography at 4 weeks post-infarction. We found that both LV systolic and diastolic function in C3KO mice was impaired compared to wild type controls. Furthermore, morphometric analysis indicates that C3KOmice have impaired regeneration and accelerated adverse remodeling, which correlates with the decrease in number of circulating stem/progenitor cells. Thus, the complement system plays an important role in mobilization of stem/progenitor cells after myocardial infarction which in turn potentially may contribute to myocardial regeneration after MI.
- © 2011 by American Heart Association, Inc.