Abstract 3334: The Beneficial Role of Endogenous Sca-1+/CD31− Cells in Post-infarction Left Ventricular Remodeling
Sca-1(Ly-6 A/E) antigen is almost universally expressed in different types of stem cells. However, the role of endogenous marrow or cardiac derived Sca-1+/CD31−/CD45− cells in post myocardial infarction (MI) left ventricular (LV) remodeling has not been well defined. We have previously reported that LV Sca-1+ protein expression and Sca-1+/CD31−/CD45− cell numbers are enhanced 7 days post-MI. Therefore, we hypothesized that endogenous marrow or cardiac originating Sca-1+/CD31−/CD45− cells contributed to physiological post-MI repair processes. The LV remodeling following MI induced by anterior descending coronary artery ligation in Sca-1 deficient mice (TG) was compared to that present in post-MI wild type mice (WT) of the same background. Ejection fraction (EF) and LV dimensions were determined by echocardiography. 4 weeks post-MI EF decreased from 57+/−1% (pre-MI) to 34+/1% (n=8, P<0.01) in WT mice and from 57+/3% to 19+/−1% in TG mice (n=8, P<0.001 vs WT). Scar sizes were larger and more severe LV remodeling was present in TG mice as compared to WT mice at 8 weeks post-MI. We also observed that vascular density was decreased in the LV peri-infarct zone of TG mice as compared with that of WT mice 4 weeks after MI. Sca-1−/CD31−cells isolated from the hearts of Sca-1 deficient mice and Sca-1 siRNA transfected Sca-1+/CD31− cells (electroporation) both had significantly reduced in vitro self-renewal capacity as compared to WT Sca-1+/CD31− cells. Unlike Sca-1+/CD31− cells, Sca-1−/CD31−cells cultured in Matrigel did not show microtubule formation. Supperarray profiling of Sca-1+/CD31− and Sca-1−/CD31− cells demonstrated an enhanced expression of cell survival genes and angiogenic factors in Sca-1+/CD31−cells. We conclude that marrow or cardiac originating Sca-1+/CD31− contribute to infarct size reduction, vasculogenesis, and decreased LV remodeling in post-MI WT mice. Hence, despite the fact that post-MI reparative processes are limited, Sca-1+/CD31− cells are crucial to those that occur.
This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).