Abstract 15908: Myocardial and Systemic Stem Cells Response to Cardiac Pressure Overload
Introduction: Aortic stenosis induces endogenous stem cell activation. We recently demonstrated an increase of cardiac stem cells (CSC) and endothelial progenitor cells (EPC) in the myocardium in response to pressure overload (PO). The goal of this study was to elucidate the sequelae of events and the cell populations involved.
Methods and Results: PO was induced using a mouse trans-aortic constriction (TAC) model. The fate of endogenous cardiac and systemic stem cells was evaluated in 8 week old TAC and sham mice. Mice were sacrificed 2, 4, 7, and 14 days post-TAC. BrdU (0.5 mg/g) was administered 17, 9, and 1 h prior to sacrifice to label proliferating cells in the 24h prior to sacrifice. EPC and SSEA1+ were analyzed by flow cytometry in the BM, spleen and heart. CSC were also examined. All data are presented as percent change relative to time matched Sham control. Heart: The peak proliferative response (including CSC and SSEA1+ cells) was 4 days post-TAC (61.2±11.9% increase in BrdU+ cells). There were no changes in EPC proliferation. The peak increase in CSC (122±71.3%), EPC (221.3±103.8%), and SSEA1+ cells (181.6±82.2%) number was 7 days post-TAC compared to Sham. Spleen: The number of EPC (-36.2±9.8%) was decreased 7 days post-TAC. We observed a biphasic loss of SSEA1+ cells at 2 and 7 days (-36.4±7% and -48.8±7.4%, respectively) post-TAC though there were no significant changes in SSEA1+ cell proliferation. Bone Marrow: EPC (-30.9±6.4%) and SSEA1+ (-90.6±21.4%) cell numbers were reduced 4 days post-TAC. Followed by a peak in proliferation at 7 days post-TAC - total BM cells (241.7±108.2%), EPC (140.3±78.5%), and SSEA1+ cells (373.6±151.7%) .
Conclusions: Our results demonstrate an orchestrated systemic stem cell response of CSC, EPC and SSEA1+ stem cells following PO. These data demonstrate there is early mobilization of EPC and SSEA1+ stem cells from the bone marrow and spleen followed by a proliferative response in the bone marrow. This mobilization combined with an early proliferative stem cell response in the myocardium leads to peak stem cell content in the myocardium at 7 days after TAC. These data identify stem cell sources and populations that could be targets for therapeutic intervention in patients with aortic stenosis and cardiac dysfunction.
- © 2011 by American Heart Association, Inc.