Abstract 11320: Reduction of Na/k-atpase Regulates Cardiac Remodeling and Regeneration in Partial Nephrectomized Mice
Reduction of Na/K-ATPase attenuates survival signaling in cardiac cells and potentiates cardiotonic steroid-induced myocyte apoptosis. This study examined the role of Na/K-ATPase in partial nephrectomized (PNx) animals using Na/K-ATPase α1 heterozygous mice (α1+/-) and their wild-type (WT) littermates. PNx was established by ligation of one branch of the left renal artery which was followed by removal of the entire decapsulated right kidney one week later. Our results indicate that PNx induces hypertension and cardiac hypertrophic growth in both α1+/- and WT mice. In point of fact, in α1+/- mice, the heart/body weight ratio was 5.0 for PNx vs 3.8 for sham, whereas in WT animals the ratio was 4.8 vs 3.8. However, immunohistological analyses indicate that PNx causes more cardiac cell apoptosis, as illustrated by the increase in active caspase 3 in the α1+/- mice. To examine if regeneration contributes to the above stated changes, cardiac tissues were probed for the progenitor cell marker c-kit and the proliferation marker ki-67. The result showed that α1+/- mice had significantly higher numbers of c-kit positive and ki-67 positive cells in their heart tissue compared to WT mice, especially in the PNx group. The majority of these c-kit positive cells (>90%) are CD45 negative, a feature that distinguishes them from hematopoietic cells. We also found that α1+/- mice in the sham group express higher levels of stem cell factor (SCF), a c-kit ligand, in their heart tissue. We conclude that PNx induces hypertrophic growth and high blood pressure regardless of Na/K-ATPase content change. However, the regeneration indicated by c-kit expression seems more active in the α1+/- mice, which may compensate for cardiac cell loss induced by PNx.
- © 2013 by American Heart Association, Inc.