Abstract 17691: Inhibition of Na/K-ATPase Signaling Regulates Cardiac C-Kit Cell Expression in Mice with Chronic Kidney Dysfunction
Introduction: Na/K-ATPase (NKA) has been shown to regulate cell survival and causes cardiac remodeling through its signaling pathway. Our previous publications have shown that genetic reduction of NKA attenuates cell survival signaling, potentiates myocyte apoptosis, and increases c-kit cell number in mice receiving 5/6th partial nephrectomy (PNx) surgery.
Hypothesis: To test if inhibition of NKA signaling increases cardiac cell death and triggers activation of c-kit cells, we subjected heterozygous mice with genetic reduction of the NKA α1 subunit (α1+/-) and their wild type (WT) litter mates to the PNx surgical model of chronic kidney disease (CKD).
Methods: Twelve weeks after PNx surgery, these mice were injected biweekly with pNaKtide, a peptide that specifically inhibits NKA related Src signaling, at a dose of 25mg/kg. Mice injected with same volume of saline were used as controls. Mice were then sacrificed 16 weeks post PNx surgery.
Results: The experimental results showed that PNx induces significant cardiac c-kit cell expression versus sham operation in α1+/- mice, but only mild changes in the WT mice. PNx also induces cardiac cell apoptosis measured by active caspase 3 staining in α1+/- mice. However, in WT mice that receive the pNaKtide injection, both caspase 3 staining and c-kit cell number in heart tissues were significantly increased compared to those injected with saline. Inhibition of NKA signaling by pNaKtide also reduces PNx induced cardiac hypertrophy in these animals. The pNaKtide injection in α1+/- mice also further increased the caspase 3 staining and c-kit cell number in the heart tissues of these animals.
Conclusions: These data suggest that cardiac cell death may trigger increases in cardiac progenitor (c-kit) cell number, whereas genetically reduction of Na/K-ATPase or injection of pNaKtide can both attenuate the signaling function of NKA in PNx animals and subsequently increase cardiac cell death.
Author Disclosures: C.A. Drummond: None. H. Shi: None. S.T. Haller: None. J. Liu: None. Z. Xie: None. C.J. Cooper: None. J.I. Shapiro: None. J.I. Shapiro: None. J. Tian: None.
- © 2014 by American Heart Association, Inc.