Reduction of Na/K-ATPase affects cardiac remodeling and increases c-kit cell abundance in partial nephrectomized mice
The current study examined the role of Na/K-ATPase α1-subunit in animals subjected to 5/6th partial nephrectomy (PNx) using Na/K-ATPase α1-heterozygous (α1(+/-)) mice and their wild-type (WT) littermates. After PNx, both WT and α1(+/-) animals displayed diastolic dimension increases, increased blood pressure, and increased cardiac hypertrophy. However, in the α1(+/-) animals we detected significant increases in cardiac cell death in PNx animals. Given that reduction of α1 elicited increased cardiac cell death with PNx, while at the same time these animals developed cardiac hypertrophy, an examination of cardiac cell number, and proliferative capabilities of those cells was carried out. Cardiac tissues were probed for the progenitor cell marker c-kit and the proliferation marker ki-67. The results revealed that α1(+/-) mice had significantly higher numbers of c-kit-positive and ki-67-positive cells, especially in the PNx group. We also found that α1(+/-) mice express higher levels of stem cell factor, a c-kit ligand, in their heart tissue and had higher circulating levels of stem cell factor than WT animals. In addition, PNx induced significant enlargement of cardiac myocytes in WT mice but has much less effect in α1(+/-) mice. However, the total cell number determined by nuclear counting is higher in α1(+/-) mice with PNx compared with WT mice. We conclude that PNx induces hypertrophic growth and high blood pressure regardless of Na/K-ATPase content change. However, total cardiac cell number as well as c-kit-positive cell number is increased in α1(+/-) mice with PNx.
Drummond CA, Sayed M, Evans KL, Shi H, Wang X, Haller ST, Liu J, Cooper CJ, Xie Z, Shapiro JI, Tian J. Reduction of Na/K-ATPase affects cardiac remodeling and increases c-kit cell abundance in partial nephrectomized mice. Am J Physiol Heart Circ Physiol. 2014;306(12):H1631-43.