Abstract P307: pNaKtide Attenuates Dyslipidemia and Atherosclerosis by Blocking Na/K- ATPase/Reactive Oxygen Species Amplification in ApoE -/- Mice

Abstract

Background: We have previously reported that the α1 subunit of the sodium potassium adenosine triphosphatase (Na/K-ATPase) acts as an amplifier for reactive oxygen species (ROS) in addition to its ion pumping function. We have also shown that blockade of this amplification with a novel peptide, pNaKtide, ameliorates oxidative stress and obesity in mice subjected to a high-fat diet. Hypothesis: Given the importance of oxidative stress in the pathophysiology of atherosclerosis, we chose to examine whether pNaKtide might be effective in ameliorating dyslipidemia and atherosclerosis in ApoE -/- mice. Methods: pNaKtide was administered in ApoE -/- mouse fed western diet. 25 mg/Kg pNaKtide was administered intraperitoneally once every 7 days. Lipid profile, glucose insulin levels, and ROS levels were measured. Aortas were dissected and quantification of aortic lesions was done. Results: Our results show that pNaKtide improved glucose tolerance and HOMA-IR scores in ApoE-/- mice fed a western diet (p<0.05). Also, pNaKtide administered to these mice significantly decreased plasma ALT, triglycerides, FFA, and LDL levels. Further, our results show that ApoE -/- mice fed a western diet had decreased plasma HDL levels and this decrease was reversed by pNaKtide. Plasma ROS levels were significantly attenuated by pNaKtide treatment. Mice fed a western diet had increased plaque size. Plaque size was significantly decreased by pNaKtide treatment. Conclusion: This study suggests that the Na/K-ATPase/ROS signaling cascade is a possible mechanism for the development of dyslipidemia and atherosclerosis associated with the metabolic syndrome phenotype and pNaKtide presents a potential novel treatment for these pathologies.